Intraocular shunt implantation

ABSTRACT

Implanting an intraocular shunt into an eye can involve creating an opening in the cornea and positioning a shunt in the anterior chamber of the eye such that the shunt terminates between layers of Tenon&#39;s capsule, thereby facilitating fluid flow out of the anterior chamber into a space between the layers of Tenon&#39;s capsule.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit of U.S. ProvisionalApplication No. 61/841,224, filed on Jun. 28, 2013, and U.S. ProvisionalApplication No. 61/895,341, filed on Oct. 24, 2013, the entirety of eachof which is incorporated herein by reference.

BACKGROUND

Field of the Inventions

The present disclosure generally relates to devices and methods ofimplanting an intraocular shunt into an eye.

Description of the Related Art

Glaucoma is a disease in which the optic nerve is damaged, leading toprogressive, irreversible loss of vision. It is typically associatedwith increased pressure of the fluid (i.e., aqueous humor) in the eye.Untreated glaucoma leads to permanent damage of the optic nerve andresultant visual field loss, which can progress to blindness. Once lost,this damaged visual field cannot be recovered. Glaucoma is the secondleading cause of blindness in the world, affecting 1 in 200 people underthe age of fifty, and 1 in 10 over the age of eighty for a total ofapproximately 70 million people worldwide.

The importance of lowering intraocular pressure (IOP) in delayingglaucomatous progression has been well documented. When drug therapyfails, or is not tolerated, surgical intervention is warranted. Surgicalfiltration methods for lowering intraocular pressure by creating a fluidflow-path between the anterior chamber and an area of lower pressurehave been described. Intraocular shunts can be positioned in the eye todrain fluid from the anterior chamber to locations such as thesub-Tenon's space, the subconjunctival space, the episcleral vein, thesuprachoroidal space, Schlemm's canal, and the intrascleral space.

Positioning of an intraocular shunt to drain fluid into the intrascleralspace is promising because it avoids contact with the conjunctiva andthe supra-choroidal space. Avoiding contact with the conjunctiva andsupra-choroid is important because it reduces irritation, inflammationand tissue reaction that can lead to fibrosis and reduce the outflowpotential of the subconjunctival and suprachoroidal space. Theconjunctiva itself plays a critical role in glaucoma filtration surgery.A less irritated and healthy conjunctiva allows drainage channels toform and less opportunity for inflammation and scar tissue formation.intrascleral shunt placement safeguards the integrity of the conjunctivaand choroid, but may provide only limited outflow pathways that mayaffect the long term IOP lowering efficacy.

SUMMARY

According to some embodiments, methods and devices are provided forpositioning an intraocular shunt within the eye to treat glaucoma.Various methods are disclosed herein which allow a clinician to create afluid pathway from the anterior chamber to an area of lower pressurewithin the eye. Although methods may be discussed in the context ofpositioning an outflow end of a shunt in a particular location (e.g.,between layers of Tenon's capsule), the methods disclosed herein can beused to create a fluid pathway in which the outflow end of the shunt ispositioned in other areas of low pressure, such as the supraciliaryspace, suprachoroidal space, the intrascleral space (i.e., betweenlayers of sclera), intra-Tenon's adhesion space (i.e., between layers ofTenon's capsule), or subconjunctival space.

For example, a method of treating glaucoma is disclosed that cancomprise inserting an intraocular shunt into eye tissue such that aninflow end of the shunt is positioned in the anterior chamber of the eyeand an outflow end of the shunt is positioned between layers of Tenon'scapsule. The shunt can comprise a lumen that extends between the inflowand outflow ends and that is configured to permit flow of aqueous humorfrom the inflow end through the shunt to the outflow end.

In accordance with some embodiments, the shunt can be introduced intothe eye through the cornea. After introducing the shunt through thecornea, the shunt can be advanced into the sclera. For example, theshunt can be advanced into the sclera through the anterior chamber angletissue.

In some embodiments, the device comprises a shaft that can be advancedinto the sclera until reaching and no further than a first position atwhich a bevel of the shaft is positioned between the layers of Tenon'scapsule.

In some embodiments, after the shaft is positioned within the sclera(e.g., after the shaft reaches the first position), a pusher componentof the device can be advanced relative to the shaft such that the shuntis pushed distally out of the shaft. Although the entire shunt can beadvanced out of the shaft by the pusher component, the method can beimplemented such that less than an entire length of the shunt is pusheddistally out of the shaft.

The device can comprise a sleeve having a lumen and a distal end. Theshaft can be received within the lumen of the sleeve.

In some embodiments, after the shaft is positioned within the sclera(e.g., after the shaft reaches the first position), the pusher componentcan be advanced to a distalmost position at which a distal end of thepusher component is positioned longitudinally proximal to the sleevedistal end. Further, the pusher component can also be advanced to adistalmost position at which a distal end of the pusher component ispositioned longitudinally adjacent to the sleeve distal end.

Further, in some embodiments, the shaft can be positioned within thesclera (e.g., after the shaft reaches the first position) such that adistal end of the sleeve is spaced apart from the eye tissue. Once theshaft is in place, the pusher component can be advanced until a distalend of the pusher component is positioned longitudinally proximal to oradjacent to the sleeve distal end or the bevel. Furthermore, after theshunt has been at least partially advanced out of the bevel, the shaftcan be proximally retracted into the sleeve. Proximal retraction of theshaft into the sleeve can be performed with the shaft maintaining itsposition relative to and within the sclera or with the sleevemaintaining its position relative to the sclera (whether spaced apartfrom the eye tissue or abutting the eye tissue), as discussed herein.

Moreover, as noted herein, some embodiments of the methods can beperformed whether the outflow end of the shunt is positioned betweenlayers of Tenon's capsule or whether the outflow end of the shunt ispositioned in another area of low pressure.

For example, referring to embodiments in which the shunt outflow end ispositioned between layers of Tenon's capsule, the device can be at thefirst position and a distal end of the sleeve can be spaced apart fromthe eye tissue, such as the anterior chamber angle tissue. Thereafter,while maintaining the position of the shaft relative to the sclera, thesleeve can be advanced distally over the shaft until the distal end ofthe sleeve contacts eye tissue, such as the anterior chamber angletissue. After the sleeve distal end contacts the tissue, the shaft canbe proximally withdrawn from the sclera until the bevel is receivedwithin a lumen of the sleeve. However, in some embodiments, the sleevedistal end can be maintained at a given position relative to the eyetissue (whether the sleeve distal end is spaced apart from or abuttingthe eye tissue) while the shaft is withdrawn into the sleeve.

In some embodiments, a method of treating glaucoma is provided that cancomprise inserting an intraocular shunt into eye tissue such that theshunt conducts fluid from the anterior chamber of the eye to a regionbetween layers of Tenon's capsule. Further, in some embodiments, themethod can comprise inserting an intraocular shunt into eye tissue suchthat the shunt conducts fluid from the anterior chamber of the eye tothe intra-Tenon's adhesion space of the eye.

The method can also be performed such that a hollow shaft is insertedinto the eye through the cornea. The shaft can be configured to hold theshunt. For example, the shaft can be enter the eye through the cornea.The intra-Tenon's adhesion space can comprise a deep layer and asuperficial layer, and an outflow end of the shunt can be positionedbetween the deep and superficial layers.

Further, a bevel of a shaft can be advanced to a position between thedeep and superficial layers, and while maintaining the bevel stationaryrelative to the eye tissue, the shunt can be distally advanced from theshaft into the intra-Tenon's adhesion space.

In accordance with some embodiments, a method of treating glaucoma isdisclosed that can comprise advancing a shaft of a device into eyetissue until a bevel of the shaft reaches a target area. Then, whilemaintaining the bevel substantially stationary relative to the targetarea, the sleeve of the device can be advanced distally over the shaftuntil a distal end of the sleeve contacts the eye tissue. Thereafter,upon contacting the sleeve distal end with the eye tissue, the shaft canbe proximally withdrawn from the eye tissue.

Additionally, while maintaining the bevel substantially stationaryrelative to the target area, a plunger can be advanced within the shaftto advance a shunt until the shunt extends into the target area. Forexample, less than an entire length of the shunt can be pushed distallyout of the shaft. The plunger can be advanced until a distal end of theplunger is positioned longitudinally adjacent to the sleeve distal end.The shunt can be introduced into the eye through the cornea. The targetarea can be selected from supraciliary space, suprachoroidal space, aspace between layers of sclera (i.e., intrascleral space), a spacebetween layers of Tenon's capsule (i.e., intra-Tenon's adhesion space),or subconjunctival space. The sleeve can be advanced between about 1 mmto about 4 mm. Further, in some embodiments, the sleeve can be advancedbetween about 2 mm to about 3 mm.

For example, in some embodiments, a method of deploying an intraocularshunt into an eye is provided. The method can comprise the steps of:inserting into the eye a hollow shaft configured to hold the intraocularshunt; and advancing the shunt from the hollow shaft such that the shuntforms a passage from the anterior chamber of the eye to theintra-Tenon's adhesion space of the eye.

The inserting step can further comprise the step of injecting an aqueoussolution into the eye. For example, the aqueous solution can be injectedbelow Tenon's capsule. The inserting step can also comprise ab internoinsertion of the hollow shaft into the eye. Ab interno insertion cancomprise inserting the hollow shaft into the eye above the corneallimbus. Further, ab interno insertion can comprise inserting the hollowshaft into the eye below the corneal limbus.

Additionally, some methods can comprise: inserting into the eye a hollowshaft configured to hold the intraocular shunt, a portion of the hollowshaft extending linearly along a longitudinal axis, and at least oneother portion of the hollow shaft extending off the longitudinal axis;and advancing the shunt from the hollow shaft such that the shunt formsa passage from the anterior chamber of the eye to the intra-Tenon'sadhesion space.

In accordance with some embodiments, a method of treating glaucoma canalso comprise inserting an intraocular shunt into eye tissue such thatan inflow end of the shunt is positioned in the anterior chamber of theeye and an outflow end of the shunt is positioned between layers ofTenon's capsule. The layers of Tenon's capsule can comprise a deep layerand a superficial layer.

Some embodiments of the methods disclosed herein such that the insertingstep can further comprise the step of injecting an aqueous solution intothe eye. For example, an aqueous solution can be injected below Tenon'scapsule. The inserting step can also comprise ab interno insertion ofthe hollow shaft into the eye. Ab interno insertion can compriseinserting the hollow shaft into the eye above the corneal limbus. Abinterno insertion can comprise inserting the hollow shaft into the eyebelow the corneal limbus.

Some embodiments of the methods disclosed herein can be implemented suchthat the inserting step comprises ab interno insertion of the hollowshaft into the eye.

Some embodiments of the methods disclosed herein can be implemented suchthat the hollow shaft is inserted into the eye without removing ananatomical feature of the eye.

The anatomical feature of the eye can be selected from the groupconsisting of: the trabecular meshwork, the iris, the cornea, and theaqueous humor. In accordance with some embodiments, the method can beperformed without inducing subconjunctival blebbing or endophthalmitis.

Additional features and advantages of the subject technology will be setforth in the description below, and in part will be apparent from thedescription, or may be learned by practice of the subject technology.The advantages of the subject technology will be realized and attainedby the structure particularly pointed out in the written description andembodiments hereof as well as the appended drawings.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory and areintended to provide further explanation of the subject technology.

BRIEF DESCRIPTION OF THE DRAWINGS

Various features of illustrative embodiments are described below withreference to the drawings. The illustrated embodiments are intended toillustrate, but not to limit, the inventions. The drawings contain thefollowing figures:

FIG. 1 provides a cross-sectional diagram of the general anatomy of theeye.

FIG. 2 is an enlarged cross-sectional diagram of the eye taken alongsection lines 2-2 of FIG. 1.

FIG. 3 depicts, implantation of an intraocular shunt with a distal endof a deployment device holding a shunt, shown in cross-section,according to some embodiments.

FIG. 4 depicts an intraocular shunt at least partially disposed within ahollow shaft of a deployment device, according to some embodiments.

FIG. 5 provides a schematic of a shunt having a flexible portion,according to some embodiments.

FIGS. 6A-6C provide schematics of a shunt implanted into an eye forregulation of fluid flow from the anterior chamber of the eye to adrainage structure of the eye, according to some embodiments.

FIG. 7A shows an embodiment of a shunt in which the proximal portion ofthe shunt includes more than one port and the distal portion of theshunt includes a single port.

FIG. 7B shows another embodiment of a shunt in which the proximalportion includes a single port and the distal portion includes more thanone port.

FIG. 7C shows another embodiment of a shunt in which the proximalportions include more than one port and the distal portions include morethan one port.

FIGS. 8A-8B show different embodiments of multi-port shunts havingdifferent diameter ports.

FIGS. 9A-9C provide schematics of shunts having a slit located along aportion of the length of the shunt, according to some embodiments.

FIG. 10 depicts a shunt having multiple slits along a length of theshunt, according to some embodiments.

FIG. 11 depicts a shunt having a slit at a proximal end of the shunt,according to some embodiments.

FIG. 12 provides a schematic of a shunt that has a variable innerdiameter, according to some embodiments.

FIGS. 13A-13D depict a shunt having multiple prongs at a distal and/orproximal end, according to some embodiments.

FIGS. 14A-14D depict a shunt having a longitudinal slit at a distaland/or proximal end, according to some embodiments.

FIG. 15 is a schematic showing an embodiment of a shunt deploymentdevice.

FIG. 16 shows an exploded view of the device shown in FIG. 16.

FIGS. 17A-17D are schematics showing different enlarged views of thedeployment mechanism of the deployment device, according to someembodiments.

FIGS. 18A-18C are schematics showing interaction of the deploymentmechanism with a portion of the housing of the deployment device,according to some embodiments.

FIG. 19 shows a cross-sectional view of the deployment mechanism of thedeployment device, according to some embodiments.

FIGS. 20A-20B show schematics of the deployment mechanism in apre-deployment configuration, according to some embodiments.

FIG. 20C shows an enlarged view of the distal portion of the deploymentdevice of FIG. 20A, with an intraocular shunt loaded within a hollowshaft of the deployment device, according to some embodiments.

FIGS. 21A-21B show schematics of the deployment mechanism at the end ofthe first stage of deployment of the shunt from the deployment device,according to some embodiments.

FIG. 21C shows an enlarged view of the distal portion of the deploymentdevice of FIG. 21A, with an intraocular shunt partially deployed fromwithin a hollow shaft of the deployment device, according to someembodiments.

FIG. 22A shows a schematic of the deployment device after deployment ofthe shunt from the device, according to some embodiments.

FIG. 22B show a schematic of the deployment mechanism at the end of thesecond stage of deployment of the shunt from the deployment device,according to some embodiments.

FIG. 22C shows an enlarged view of the distal portion of the deploymentdevice after retraction of the shaft with the pusher abutting the shunt,according to some embodiments.

FIG. 22D shows an enlarged view of the distal portion of the deploymentdevice after deployment of the shunt, according to some embodiments.

FIGS. 23-30 depict a sequence for ab interno shunt placement, accordingto some embodiments.

FIG. 31 depicts an implanted shunt in an S-shaped scleral passageway,according to some embodiments.

FIG. 32 depicts an example of a hollow shaft configured to hold anintraocular shunt fully within the shaft, according to some embodiments.

FIGS. 33-39 depict a sequence for ab externo shunt placement, accordingto some embodiments.

FIGS. 40-41 depict a sequence for ab externo insertion of a shaft of adeployment device using an applicator, according to some embodiments.

FIG. 42 depicts deployment of the shunt in the intra scleral space wherea distal end of the shunt is flush with the sclera surface, according tosome embodiments.

FIG. 43 depicts deployment of the shunt in the intra scleral space wherea distal end of the shunt is about 200-500 micron behind the scleralexit, according to some embodiments.

FIG. 44 depicts deployment of the shunt in the intra scleral space wherea distal end of the shunt is more than about 500 micron behind thescleral exit, according to some embodiments.

FIG. 45 depicts placement of a shunt in the supraciliary space,according to some embodiments.

FIG. 46 depicts placement of a shunt in the suprachoroidal space,according to some embodiments.

FIG. 47 depicts placement of a shunt in the subconjunctival space,according to some embodiments.

FIG. 48 depicts placement of a shunt in the intrascleral space,according to some embodiments.

FIG. 49 depicts placement of a shunt in the intra-Tenon's adhesionspace, according to some embodiments.

FIG. 50 is an enlarged schematic cross-sectional view taken alongsection 50 of FIG. 49.

FIG. 51 is a perspective view taken along section lines 51-51 of FIG.50.

FIGS. 52A-52E depict an intraocular shunt being deployed within the eye,according to another embodiment.

FIGS. 53A-53E depict an intraocular shunt being deployed within the eye,according to yet another embodiment.

FIGS. 54A-54E depict an intraocular shunt being deployed within the eye,according to yet another embodiment.

DETAILED DESCRIPTION

In the following detailed description, numerous specific details are setforth to provide a full understanding of the subject technology. Itshould be understood that the subject technology may be practicedwithout some of these specific details. In other instances, well-knownstructures and techniques have not been shown in detail so as not toobscure the subject technology.

Further, while the present description sets forth specific details ofvarious embodiments, it will be appreciated that the description isillustrative only and should not be construed in any way as limiting.Additionally, it is contemplated that although some embodiments may bedisclosed or shown in the context of ab interno procedures, suchembodiments can be used in ab externo procedures. Furthermore, variousapplications of such embodiments and modifications thereto, which mayoccur to those who are skilled in the art, are also encompassed by thegeneral concepts described herein.

Glaucoma is a disease in which the optic nerve is damaged, leading toprogressive, irreversible loss of vision. It is typically associatedwith increased pressure of the fluid (i.e., aqueous humor) in the eye.Untreated glaucoma leads to permanent damage of the optic nerve andresultant visual field loss, which can progress to blindness. Once lost,this damaged visual field cannot be recovered.

In conditions of glaucoma, the pressure of the aqueous humor in the eye(anterior chamber) increases and this resultant increase of pressure cancause damage to the vascular system at the back of the eye andespecially to the optic nerve. The treatment of glaucoma and otherdiseases that lead to elevated pressure in the anterior chamber involvesrelieving pressure within the anterior chamber to a normal level.

Glaucoma filtration surgery is a surgical procedure typically used totreat glaucoma. The procedure involves placing a shunt in the eye torelieve intraocular pressure by creating a pathway for draining aqueoushumor from the anterior chamber of the eye. The shunt is typicallypositioned in the eye such that it creates a drainage pathway betweenthe anterior chamber of the eye and a region of lower pressure. Variousstructures and/or regions of the eye having lower pressure that havebeen targeted for aqueous humor drainage include Schlemm's canal, thesubconjunctival space, the episcleral vein, the suprachoroidal space, orthe subarachnoid space. Methods of implanting intraocular shunts areknown in the art. Shunts may be implanted using an ab externo approach(entering through the conjunctiva and inwards through the sclera) or anab interno approach (entering through the cornea, across the anteriorchamber, through the trabecular meshwork and sclera).

FIG. 1 provides a schematic diagram of the general anatomy of the eye.An anterior aspect of the anterior chamber 1 of the eye is the cornea 2,and a posterior aspect of the anterior chamber 1 of the eye is the iris4. Beneath the iris 4 is the lens 5. The anterior chamber 1 is filledwith aqueous humor 3. The aqueous humor 3 drains into a space(s) 6 deepto the conjunctiva 7 through the trabecular meshwork (not shown indetail) of the sclera 8. The aqueous humor is drained from the space(s)6 deep to the conjunctiva 7 through a venous drainage system (notshown).

FIG. 2 is an enlarged view of the schematic diagram of FIG. 1 takenalong section lines 2-2. FIG. 2 illustrates a detail view of the sclera8 and surrounding tissue. As shown, the conjunctiva 7 attaches to thesclera 8 at the limbus 9.

Deep to the conjunctiva 7 is Tenon's capsule 10, sometimes referred toas Tenon's membrane or Tenon's tendon. Tenon's capsule 10 comprises twolayers (i.e., superficial and deep layers) and an intra-Tenon's adhesionspace 10 that extends between the superficial and deep layers of Tenon'scapsule 10. The intra-Tenon's adhesion space 11 surrounds the eyecircumferentially. The intra-Tenon's adhesion space 11 can extend aroundthe eye posterior to the limbus 9.

In the view of FIG. 2, deep to the intra-Tenon's adhesion space 11 is arectus muscle 20. The eye has four rectus muscles (superior, inferior,lateral, and medial) that attach to sclera via a rectus tendon. FIG. 2illustrates that the rectus muscle 20 attaches to the sclera 8 via arectus tendon 22. For illustration purposes, the rectus tendon 22 isshown inserting onto the sclera 8. In some cases, there may not be aclear insertion point of the rectus tendon 22 onto the sclera 8, butthere will be a gradual transition between the rectus tendon 22 and theintra-Tenon's adhesion space 11.

Additionally, as illustrated in FIG. 1, Tenon's capsule 10 and theintra-Tenon's adhesion space 11 is illustrated extending anteriorlyrelative to and superficial to the rectus muscle 20. As also shown,posterior to the rectus tendon, Tenon's capsule 10 and the intra-Tenon'sadhesion space 11 also extend deep to and around the rectus muscle 20.In this region, there is a reflection of Tenon's capsule 10 and theintra-Tenon's adhesion space 11 from the rectus muscle 20 onto the globeor sclera 8. Thus, Tenon's capsule 10 and the intra-Tenon's adhesionspace 11 envelop or encapsulate the rectus muscle 20.

FIG. 2 illustrates that in some locations, Tenon's capsule 10, and thus,the intra-Tenon's adhesion space 11, surrounds a rectus muscle 20.According to some embodiments of the methods disclosed herein, theintra-Tenon's adhesion space 11 can be accessed from the anteriorchamber 1. Tenon's capsule 10 and the intra-Tenon's adhesion space 11surround the eye circumferentially.

FIG. 2 also illustrates the drainage channels of the eye, includingSchlemm's canal 30 and the trabecular meshwork 32, which extend throughthe sclera 8. Further, deep to the sclera 8, the ciliary body 34 is alsoshown. The ciliary body 34 transitions posteriorly to the choroid 40.Deep to the limbus 9 is a scleral spur 36. The scleral spur 36 extendscircumferentially within the anterior chamber 1 of the eye. Further, thescleral spur 36 is disposed anteriorly to the anterior chamber angle 38.Furthermore, “anterior chamber angle tissue” can refer to the eye tissuein the region extending along and/or including one or more of the cornea2, the sclera 8, Schlemm's canal 30, the trabecular meshwork 32, theciliary body 34, the iris 35, or the scleral spur 36.

Accordingly, for definitional purposes, the space between theconjunctiva 7 and Tenon's capsule or the intra-Tenon's adhesion space 11is referred to herein as subconjunctival space 332 (here shown as apotential space). Further, the space within a deep layer 360 and asuperficial layer 370 of Tenon's capsule 10 is referred to herein as theintra-Tenon's adhesion space 11. Additionally, the space within thesclera 8 (i.e., between the superficial and deep layers of the sclera 8)is referred to herein as intrascleral space 342 (here shown as apotential space). The space between the sclera 8 and the ciliary body 34is referred to herein as supraciliary space 310 (here shown as apotential space). Finally, the space between the sclera 8 and thechoroid 40 is referred to as suprachoroidal space 322 (here shown as apotential space). The supraciliary space 310 can be continuous with thesuprachoroidal space 322.

Ab interno approaches for implanting an intraocular shunt in thesubconjunctival space are shown for example in Yu et al. (U.S. Pat. No.6,544,249 and U.S. Patent Publication No. 2008/0108933) and Prywes (U.S.Pat. No. 6,007,511), the contents of each of which are incorporated byreference herein in its entirety. Briefly and with reference to FIG. 3,a surgical intervention to implant the shunt involves inserting into theeye a deployment device 115 that holds an intraocular shunt, anddeploying the shunt within the eye 116. A deployment device 115 holdingthe shunt enters the eye 116 through the cornea 117 (ab internoapproach). The deployment device 115 is advanced across the anteriorchamber 120 (as depicted by the broken line) in what is referred to as atranspupil implant insertion. The deployment device 115 is advancedthrough the sclera 121 until a distal portion of the device is inproximity to the subconjunctival space 118 deep to the conjunctiva 119.The shunt is then deployed from the deployment device, producing aconduit between the anterior chamber and the subconjunctival space toallow aqueous humor to drain through the conjunctival lymphatic system.

While such ab interno subconjunctival filtration procedures have beensuccessful in relieving intraocular pressure, there is a substantialrisk that the intraocular shunt may be deployed too close to theconjunctiva, resulting in irritation and subsequent inflammation and/orscarring of the conjunctiva, which can cause the glaucoma filtrationprocedure to fail (See Yu et al., Progress in Retinal and Eye Research,28:303-325 (2009)). Additionally, commercially available shunts that arecurrently utilized in such procedures are not ideal for ab internosubconjunctival placement due to the length of the shunt (i.e., toolong) and/or the materials used to make the shunt (e.g., gold, polymer,titanium, or stainless steel), and can cause significant irritation tothe tissue surrounding the shunt, as well as the conjunctiva, ifdeployed too close.

The present disclosure provides methods for implanting intraocularshunts within the sclera (i.e., intrascleral implantation) and are thussuitable for use in an glaucoma filtration procedure (ab interno or abexterno). In some embodiments of the methods disclosed herein, theimplanted shunt forms a passage from the anterior chamber of the eyeinto the sclera (i.e., intrascleral space). Design and/or deployment ofan intraocular shunt such that the inlet terminates in the anteriorchamber and the outlet terminates intrascleral safeguard the integrityof the conjunctiva to allow subconjunctival drainage pathways tosuccessfully form. Additionally, drainage into the intrascleral spaceprovides access to more lymphatic channels than just the conjunctivallymphatic system, such as the episcleral lymphatic network.

Additionally, some embodiments of the methods disclosed herein recognizethat while intrascleral shunt placement avoids contact with theconjunctiva, fluid outflow from the shunt into the intrascleral spacemay overwhelm the natural drainage structures (e.g., the episcleralvessel complex) proximate the intrascleral space. According to someembodiments, the present disclosure can combine intrascleral shuntplacement with creation of a passageway through the sclera, therebyfacilitating fluid drainage from the intrascleral space. Such apassageway facilitates diffusion of fluid into the subconjunctival andsuprachoroidal spaces. Accordingly, the advantages of intrascleral shuntplacement are recognized and the additional drainage passageway preventsthe natural drainage structures proximate the intrascleral space frombecoming overwhelmed with fluid output from the shunt.

Embodiments of Intraocular Shunts

According to some embodiments, the present disclosure providesintraocular shunts that are configured to form a drainage pathway fromthe anterior chamber of the eye to the intrascleral space. Inparticular, according to some embodiments, the intraocular shunts have alength that is sufficient to form a drainage pathway from the anteriorchamber of the eye to the intrascleral space. The length of the shunt isimportant for achieving placement specifically in the intrascleralspace. A shunt that is too long will extend beyond the intrascleralspace and irritate the conjunctiva which can cause the filtrationprocedure to fail, as previously described. A shunt that is too shortwill not provide sufficient access to drainage pathways such as theepiscleral lymphatic system or the conjunctival lymphatic system.

According to some embodiments, shunts used in methods disclosed hereinmay be any length that allows for drainage of aqueous humor from ananterior chamber of an eye to the intrascleral space. Exemplary shuntsrange in length from about 1 mm to about 10 mm or between about 2 mm toabout 6 mm, or any specific value within said ranges. In certainembodiments, the length of the shunt is between about 2 mm to about 4mm, or any specific value within said range. According to someembodiments, the intraocular shunts disclosed herein can be particularlysuitable for use in an ab intern glaucoma filtration procedure.Commercially available shunts that are currently used in ab internfiltration procedures are typically made of a hard, inflexible materialsuch as gold, polymer, titanium, or stainless steel, and causesubstantial irritation of the eye tissue, resulting in ocularinflammation such as subconjunctival blebbing or endophthalmitis. Someembodiments of the methods disclosed herein may be conducted using anycommercially available shunts, such as the Optonol Ex-PRESS™ miniGlaucoma shunt, and the Solx DeepLight Gold™ Micro-Shunt.

In some embodiments, the intraocular shunts disclosed herein can beflexible, and have an elasticity modulus that is substantially identicalto the elasticity modulus of the surrounding tissue in the implant site.As such, some embodiments of the intraocular shunts disclosed herein canbe easily bendable, do not erode or cause a tissue reaction, and do notmigrate once implanted. Thus, when implanted in the eye using an abinterno procedure, such as the methods described herein, someembodiments of the intraocular shunts disclosed herein do not inducesubstantial ocular inflammation such as subconjunctival blebbing orendophthalmitis. Additional exemplary features of some embodiments ofintraocular shunts are discussed in further detail below.

Tissue Compatible Shunts

In certain aspects, the present disclosure generally provides shuntscomposed of a material that has an elasticity modulus that is compatiblewith an elasticity modulus of tissue surrounding the shunt. In thismanner, some embodiments of the shunts can be flexibility matched withthe surrounding tissue, and thus will remain in place after implantationwithout the need for any type of anchor that interacts with thesurrounding tissue. Consequently, some embodiments of the shunt willmaintain fluid flow away for an anterior chamber of the eye afterimplantation without causing irritation or inflammation to the tissuesurrounding the eye.

Elastic modulus, or modulus of elasticity, is a mathematical descriptionof an object or substance's tendency to be deformed elastically when aforce is applied to it. The elastic modulus of an object is defined asthe slope of its stress-strain curve in the elastic deformation region:

$\lambda\overset{def}{=}\frac{Stress}{Strain}$where lambda (λ) is the elastic modulus, stress is the force causing thedeformation divided by the area to which the force is applied; andstrain is the ratio of the change caused by the stress to the originalstate of the object. The elasticity modulus may also be known as Young'smodulus (E), which describes tensile elasticity, or the tendency of anobject to deform along an axis when opposing forces are applied alongthat axis. Young's modulus is defined as the ratio of tensile stress totensile strain. For further description regarding elasticity modulus andYoung's modulus, see for example Gere (Mechanics of Materials, 6thEdition, 2004, Thomson), the content of which is incorporated byreference herein in its entirety.

The elasticity modulus of any tissue can be determined by one of skillin the art. See for example Samani et al. (Phys. Med. Biol. 48:2183,2003); Erkamp et al. (Measuring The Elastic Modulus Of Small TissueSamples, Biomedical Engineering Department and Electrical Engineeringand Computer Science Department University of Michigan Ann Arbor, Mich.48109-2125; and Institute of Mathematical Problems in Biology RussianAcademy of Sciences, Pushchino, Moscow Region 142292 Russia); Chen etal. (IEEE Trans. Ultrason. Ferroelec. Freq. Control 43:191-194, 1996);Hall, (In 1996 Ultrasonics Symposium Proc., pp. 1193-1196, IEEE Cat. No.96CH35993, IEEE, New York, 1996); and Parker (Ultrasound Med. Biol.16:241-246, 1990), each of which provides methods of determining theelasticity modulus of body tissues. The content of each of these isincorporated by reference herein in its entirety.

The elasticity modulus of tissues of different organs is known in theart. For example, Pierscionek et al. (Br J Ophthalmol, 91:801-803, 2007)and Friberg (Experimental Eye Research, 473:429-436, 1988) show theelasticity modulus of the cornea and the sclera of the eye. The contentof each of these references is incorporated by reference herein in itsentirety. Chen, Hall, and Parker show the elasticity modulus ofdifferent muscles and the liver. Erkamp shows the elasticity modulus ofthe kidney.

Some embodiments of the shunts can be composed of a material that iscompatible with an elasticity modulus of tissue surrounding the shunt.In certain embodiments, the material has an elasticity modulus that issubstantially identical to the elasticity modulus of the tissuesurrounding the shunt. In other embodiments, the material has anelasticity modulus that is greater than the elasticity modulus of thetissue surrounding the shunt. Exemplary materials includes biocompatiblepolymers, such as polycarbonate, polyethylene, polyethyleneterephthalate, polyimide, polystyrene, polypropylene,poly(styrene-b-isobutylene-b-styrene), or silicone rubber.

In some embodiments, the shunt can be composed of a material that has anelasticity modulus that is compatible with the elasticity modulus oftissue in the eye, particularly scleral tissue. In certain embodiments,compatible materials are those materials that are softer than scleraltissue or marginally harder than scleral tissue, yet soft enough toprohibit shunt migration. The elasticity modulus for anterior scleraltissue is about 2.9±1.4×106 N/m2, and 1.8±1.1×106 N/m2 for posteriorscleral tissue. See Friberg (Experimental Eye Research, 473:429-436,1988). An exemplary material is cross linked gelatin derived from Bovineor Porcine Collagen.

The present disclosure encompasses shunts of different shapes anddifferent dimensions, and some embodiments of the shunts disclosedherein may be any shape or any dimension that may be accommodated by theeye. In certain embodiments, the intraocular shunt is of a cylindricalshape and has an outside cylindrical wall and a hollow interior. Theshunt may have an inside diameter from about 10 μm to about 250 μm, anoutside diameter from about 100 μm to about 450 μm, and a length fromabout 2 mm to about 10 mm.

Shunts Reactive to Pressure

In other aspects, the present disclosure generally provides shunts inwhich a portion of the shunt is composed of a flexible material that isreactive to pressure, i.e., the diameter of the flexible portion of theshunt fluctuates depending upon the pressures exerted on that portion ofthe shunt. FIG. 5 provides a schematic of a shunt 123 having a flexibleportion 151. In this figure, the flexible portion 151 is shown in themiddle of the shunt 123. However, the flexible portion 151 may belocated in any portion of the shunt, such as the proximal or distalportion of the shunt. In certain embodiments, the entire shunt iscomposed of the flexible material, and thus the entire shunt is flexibleand reactive to pressure.

The flexible portion 151 of the shunt 123 acts as a valve that regulatesfluid flow through the shunt. The human eye produces aqueous humor at arate of about 2 μl/min for about 3 ml/day. The entire aqueous volume isabout 0.25 ml. When the pressure in the anterior chamber falls aftersurgery to about 7 mmHg to about 8 mmHg, it is assumed the majority ofthe aqueous humor is exiting the eye through the implant since venousbackpressure prevents any significant outflow through normal drainagestructures (e.g., the trabecular meshwork).

After implantation, intraocular shunts have pressure exerted upon themby tissues surrounding the shunt (e.g., scleral tissue such as thesclera channel and the sclera exit) and pressure exerted upon them byaqueous humor flowing through the shunt. The flow through the shunt, andthus the pressure exerted by the fluid on the shunt, is calculated bythe equation:

$\Phi = {\frac{dV}{dT} = {{v\;\pi\; R^{2}} = {{\frac{\pi\; R^{4}}{8\;\eta}\left( \frac{{- \Delta}\; P}{\Delta\; x} \right)} = {\frac{\pi\; R^{4}}{8\;\eta}\frac{{\Delta\; P}}{L}}}}}$

where Φ is the volumetric flow rate; V is a volume of the liquid poured(cubic meters); t is the time (seconds); v is mean fluid velocity alongthe length of the tube (meters/second); x is a distance in direction offlow (meters); R is the internal radius of the tube (meters); ΔP is thepressure difference between the two ends (pascals); η is the dynamicfluid viscosity (pascal-second (Pa·s)); and L is the total length of thetube in the x direction (meters).

FIG. 6A provides a schematic of a shunt 126 implanted into an eye forregulation of fluid flow from the anterior chamber of the eye to an areaof lower pressure (e.g., the intrascleral space). The shunt is implantedsuch that a proximal end 127 of the shunt 126 resides in the anteriorchamber 128 of the eye, and a distal end 129 of the shunt 126 residesoutside of the anterior chamber to conduct aqueous humor from theanterior chamber to an area of lower pressure. A flexible portion 130 ofthe shunt 126 spans at least a portion of the sclera of the eye. Asshown in FIG. 6A, the flexible portion spans an entire length of thesclera 131.

When the pressure exerted on the flexible portion 130 of the shunt 126by sclera 131 (vertical arrows) is greater than the pressure exerted onthe flexible portion 130 of the shunt 126 by the fluid flowing throughthe shunt (horizontal arrow), the flexible portion 130 decreases indiameter, restricting flow through the shunt 126 (FIG. 6B). Therestricted flow results in aqueous humor leaving the anterior chamber128 at a reduced rate.

When the pressure exerted on the flexible portion 130 of the shunt 126by the fluid flowing through the shunt (horizontal arrow) is greaterthan the pressure exerted on the flexible portion 130 of the shunt 126by the sclera 131 (vertical arrows), the flexible portion 130 increasesin diameter, increasing flow through the shunt 126 (FIG. 6C). Theincreased flow results in aqueous humor leaving the anterior chamber 128at an increased rate.

The present disclosure encompasses shunts of different shapes anddifferent dimensions, and some embodiments of the shunts disclosedherein may be any shape or any dimension that may be accommodated by theeye. In certain embodiments, the intraocular shunt is of a cylindricalshape and has an outside cylindrical wall and a hollow interior. Theshunt may have an inside diameter from about 10 μm to about 250 μm, anoutside diameter from about 100 μm to about 450 μm, and a length fromabout 2 mm to about 10 mm.

In some embodiments, the shunt has a length of about 6 mm and an innerdiameter of about 64 μm. With these dimensions, the pressure differencebetween the proximal end of the shunt that resides in the anteriorchamber and the distal end of the shunt that resides outside theanterior chamber is about 4.3 mmHg. Such dimensions thus allow theimplant to act as a controlled valve and protect the integrity of theanterior chamber.

It will be appreciated that different dimensioned implants may be used.For example, shunts that range in length from about 2 mm to about 10 mmand have a range in inner diameter from about 10 μm to about 100 μmallow for pressure control from about 0.5 mmHg to about 20 mmHg.

The material of the flexible portion and the thickness of the wall ofthe flexible portion will determine how reactive the flexible portion isto the pressures exerted upon it by the surrounding tissue and the fluidflowing through the shunt. Generally, with a certain material, thethicker the flexible portion, the less responsive the portion will be topressure. In certain embodiments, the flexible portion is a gelatin orother similar material, and the thickness of the gelatin materialforming the wall of the flexible portion ranges from about 10 μm thickto about 100 μm thick.

In a certain embodiment, the gelatin used for making the flexibleportion is known as gelatin Type B from bovine skin. An exemplarygelatin is PB Leiner gelatin from bovine skin, Type B, 225 Bloom, USP.Another material that may be used in the making of the flexible isavailable from Sigma Chemical Company of St. Louis, Mo. under CodeG-9382. Still other suitable gelatins include bovine bone gelatin,porcine bone gelatin and human-derived gelatins. In addition togelatins, the flexible portion may be made of hydroxypropylmethylcellulose (HPMC), collagen, polylactic acid, polylglycolic acid,hyaluronic acid and glycosaminoglycans.

In certain embodiments, the gelatin is cross-linked. Cross-linkingincreases the inter- and intramolecular binding of the gelatinsubstrate. Any method for cross-linking the gelatin may be used. In someembodiments, the formed gelatin is treated with a solution of across-linking agent such as, but not limited to, glutaraldehyde. Othersuitable compounds for cross-linking include1-ethyl-3-(3-(dimethylaminopropyl)carbodiimide (EDC). Cross-linking byradiation, such as gamma or electron beam (e-beam) may be alternativelyemployed.

In one embodiment, the gelatin is contacted with a solution of about 25%glutaraldehyde for a selected period of time. One suitable form ofglutaraldehyde is a grade 1G5882 glutaraldehyde available from SigmaAldridge Company of Germany, although other glutaraldehyde solutions mayalso be used. The pH of the glutaraldehyde solution should be in therange of about 7 to about 7.8 and, more particularly, about 7.35 toabout 7.44 and typically about 7.4+/−0.01. If necessary, the pH may beadjusted by adding a suitable amount of a base such as sodium hydroxideas needed.

Methods for forming the flexible portion of the shunt are shown forexample in Yu et al. (U.S. patent application number 2008/0108933), thecontent of which is incorporated by reference herein in its entirety. Inan exemplary protocol, the flexible portion may be made by dipping acore or substrate such as a wire of a suitable diameter in a solution ofgelatin. The gelatin solution is typically prepared by dissolving agelatin powder in de-ionized water or sterile water for injection andplacing the dissolved gelatin in a water bath at a temperature of about55° C. with thorough mixing to ensure complete dissolution of thegelatin. In one embodiment, the ratio of solid gelatin to water is about10% to about 50% gelatin by weight to about 50% to about 90% by weightof water. In an embodiment, the gelatin solution includes about 40% byweight, gelatin dissolved in water. The resulting gelatin solutionshould be devoid of air bubbles and has a viscosity that is betweenabout 200 centipoise (“cp”) to about 500 cp and more particularlybetween about 260 cp and about 410 cp.

Once the gelatin solution has been prepared, in accordance with themethod described above, supporting structures such as wires having aselected diameter are dipped into the solution to form the flexibleportion. Stainless steel wires coated with a biocompatible, lubriciousmaterial such as polytetrafluoroethylene (Teflon) are preferred.

Typically, the wires are gently lowered into a container of the gelatinsolution and then slowly withdrawn. The rate of movement is selected tocontrol the thickness of the coat. In addition, it is preferred that thetube be removed at a constant rate in order to provide the desiredcoating. To ensure that the gelatin is spread evenly over the surface ofthe wire, in one embodiment, the wires may be rotated in a stream ofcool air which helps to set the gelatin solution and affix film onto thewire. Dipping and withdrawing the wire supports may be repeated severaltimes to further ensure even coating of the gelatin. Once the wires havebeen sufficiently coated with gelatin, the resulting gelatin films onthe wire may be dried at room temperature for at least 1 hour, and morepreferably, about 10 hours to about 24 hours. Apparatus for forminggelatin tubes are described in Yu et al. (U.S. patent application number2008/0108933).

Once dried, the formed flexible portions may be treated with across-linking agent. In one embodiment, the formed flexible portion maybe cross-linked by dipping the wire (with film thereon) into the 25%glutaraldehyde solution, at pH of from about 7.0 to about 7.8 and morepreferably from about 7.35 to about 7.44 at room temperature for atleast about 4 hours and preferably from about 10 to about 36 hours,depending on the degree of cross-linking desired. In one embodiment, theformed flexible portion is contacted with a cross-linking agent such asglutaraldehyde for at least about 16 hours. Cross-linking can also beaccelerated when it is performed a high temperatures. It is believedthat the degree of cross-linking is proportional to the bioabsorptiontime of the shunt once implanted. In general, the more cross-linking,the longer the survival of the shunt in the body.

The residual glutaraldehyde or other cross-linking agent is removed fromthe formed flexible portion by soaking the tubes in a volume of sterilewater for injection. The water may optionally be replaced at regularintervals, circulated or re-circulated to accelerate diffusion of theunbound glutaraldehyde from the tube. The tubes are washed for a periodof a few hours to a period of a few months with the ideal time beingfrom about 3 days to about 14 days. The now cross-linked gelatin tubesmay then be dried (cured) at ambient temperature for a selected periodof time. It has been observed that a drying period of from about 48 toabout 96 hours and more typically 3 days (i.e., 72 hours) may bepreferred for the formation of the cross-linked gelatin tubes.

Where a cross-linking agent is used, it may be desirable to include aquenching agent in the method of making the flexible portion. Quenchingagents remove unbound molecules of the cross-linking agent from theformed flexible portion. In certain cases, removing the cross-linkingagent may reduce the potential toxicity to a patient if too much of thecross-linking agent is released from the flexible portion. In certainembodiments, the formed flexible portion is contacted with the quenchingagent after the cross-linking treatment and, may be included with thewashing/rinsing solution. Examples of quenching agents include glycineor sodium borohydride.

After the requisite drying period, the formed and cross-linked flexibleportion is removed from the underlying supports or wires. In oneembodiment, wire tubes may be cut at two ends and the formed gelatinflexible portion slowly removed from the wire support. In anotherembodiment, wires with gelatin film thereon may be pushed off using aplunger or tube to remove the formed gelatin flexible portion.

Multi-Port Shunts

Other aspects of the present disclosure generally provide multi-portshunts. Such shunts reduce probability of the shunt clogging afterimplantation because fluid can enter or exit the shunt even if one ormore ports of the shunt become clogged with particulate. In certainembodiments, the shunt includes a hollow body defining a flow path andmore than two ports, in which the body is configured such that aproximal portion receives fluid from the anterior chamber of an eye anda distal portion directs the fluid to drainage structures associatedwith the intrascleral space.

The shunt may have many different configurations. FIG. 7A shows anembodiment of a shunt 132 in which the proximal portion of the shunt(i.e., the portion disposed within the anterior chamber of the eye)includes more than one port (designated as numbers 133 a to 133 e) andthe distal portion of the shunt (i.e., the portion that is located inthe intrascleral space) includes a single port 134. FIG. 7B showsanother embodiment of a shunt 132 in which the proximal portion includesa single port 133 and the distal portion includes more than one port(designated as numbers 134 a to 134 e). FIG. 7C shows another embodimentof a shunt 132 in which the proximal portions include more than one port(designated as numbers 133 a to 133 e) and the distal portions includemore than one port (designated as numbers 134 a to 134 e). While FIGS.7A-7C show shunts having ports at the proximal portion, distal portion,or both, those shunts are only exemplary embodiments. The ports may belocated along any portion of the shunt, and some embodiments of theshunts disclosed herein include all shunts having more than two ports.For example, some embodiments of the shunts disclosed herein may includeat least three ports, at least four ports, at least five ports, at least10 ports, at least 15 ports, or at least 20 ports.

The ports may be positioned in various different orientations and alongvarious different portions of the shunt. In certain embodiments, atleast one of the ports is oriented at an angle to the length of thebody. In certain embodiments, at least one of the ports is oriented 90°to the length of the body. See for example FIG. 7A, which depicts ports133 a, 133 b, 133 d, and 133 e as being oriented at a 90° angle to port133 c.

The ports may have the same or different inner diameters. In certainembodiments, at least one of the ports has an inner diameter that isdifferent from the inner diameters of the other ports. FIGS. 8A and 8Bshow an embodiment of a shunt 132 having multiple ports (133 a and 133b) at a proximal end and a single port 134 at a distal end. FIG. 8Ashows that port 133 b has an inner diameter that is different from theinner diameters of ports 133 a and 134. In this figure, the innerdiameter of port 133 b is less than the inner diameter of ports 133 aand 134. An exemplary inner diameter of port 133 b is from about 20 μmto about 40 μm, particularly about 30 μm. In other embodiments, theinner diameter of port 133 b is greater than the inner diameter of ports133 a and 134. See, for example, FIG. 8B.

The present disclosure encompasses shunts of different shapes anddifferent dimensions, and the some embodiments of the shunts disclosedherein may be any shape or any dimension that may be accommodated by theeye. In certain embodiments, the intraocular shunt is of a cylindricalshape and has an outside cylindrical wall and a hollow interior. Theshunt may have an inside diameter from about 10 μm to about 250 μm, anoutside diameter from about 100 μm to about 450 μm, and a length fromabout 0.5 mm to about 20 mm. Some embodiments of the shunts disclosedherein may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts with Overflow Ports

Other aspects of the present disclosure generally provide shunts withoverflow ports. Those shunts are configured such that the overflow portremains partially or completely closed until there is a pressurebuild-up within the shunt sufficient to force open the overflow port.Such pressure build-up typically results from particulate partially orfully clogging an entry or an exit port of the shunt. Such shunts reduceprobability of the shunt clogging after implantation because fluid canenter or exit the shunt by the overflow port even if one port of theshunt becomes clogged with particulate.

In certain embodiments, the shunt includes a hollow body defining aninlet configured to receive fluid from an anterior chamber of an eye andan outlet configured to direct the fluid to the intrascleral space, thebody further including at least one slit. The slit may be located at anyplace along the body of the shunt. FIG. 9A shows a shunt 135 having aninlet 136, an outlet 137, and a slit 138 located in proximity to theinlet 136. FIG. 9B shows a shunt 135 having an inlet 136, an outlet 137,and a slit 139 located in proximity to the outlet 137. FIG. 9C shows ashunt 135 having an inlet 136, an outlet 137, a slit 138 located inproximity to the inlet 136, and a slit 139 located in proximity to theoutlet 137.

While FIGS. 9A-9C show shunts have only a single overflow port at theproximal portion, the distal portion, or both the proximal and distalportions, those shunts are only exemplary embodiments. The overflowport(s) may be located along any portion of the shunt, and someembodiments of the shunts disclosed herein include shunts having morethan one overflow port. In certain embodiments, some embodiments of theshunts disclosed herein include more than one overflow port at theproximal portion, the distal portion, or both. For example, FIG. 10shows a shunt 140 having an inlet 141, an outlet 142, and slits 143 aand 143 b located in proximity to the inlet 141. Some embodiments of theshunts disclosed herein may include at least two overflow ports, atleast three overflow ports, at least four overflow ports, at least fiveoverflow ports, at least 10 overflow ports, at least 15 overflow ports,or at least 20 overflow ports. In certain embodiments, some embodimentsof the shunts disclosed herein include two slits that overlap and areoriented at 90° to each other, thereby forming a cross.

In certain embodiments, the slit may be at the proximal or the distalend of the shunt, producing a split in the proximal or the distal end ofthe implant. FIG. 11 shows an embodiment of a shunt 144 having an inlet145, outlet 146, and a slit 147 that is located at the proximal end ofthe shunt, producing a split in the inlet 145 of the shunt.

In certain embodiments, the slit has a width that is substantially thesame or less than an inner diameter of the inlet. In other embodiments,the slit has a width that is substantially the same or less than aninner diameter of the outlet. In certain embodiments, the slit has alength that ranges from about 0.05 mm to about 2 mm, and a width thatranges from about 10 μm to about 200 μm. Generally, the slit does notdirect the fluid unless the outlet is obstructed. However, the shunt maybe configured such that the slit does direct at least some of the fluideven if the inlet or outlet is not obstructed.

The present disclosure encompasses shunts of different shapes anddifferent dimensions, and some embodiments of the shunts disclosedherein may be any shape or any dimension that may be accommodated by theeye. In certain embodiments, the intraocular shunt is of a cylindricalshape and has an outside cylindrical wall and a hollow interior. Theshunt may have an inside diameter from about 10 μm to about 250 μm, anoutside diameter from about 100 μm to about 450 μm, and a length fromabout 2 mm to about 10 mm. Some embodiments of the shunts disclosedherein may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts Having a Variable Inner Diameter

In other aspects, the present disclosure generally provides a shunthaving a variable inner diameter. In some embodiments, the diameterincreases from inlet to outlet of the shunt. By having a variable innerdiameter that increases from inlet to outlet, a pressure gradient isproduced and particulate that may otherwise clog the inlet of the shuntis forced through the inlet due to the pressure gradient. Further, theparticulate will flow out of the shunt because the diameter onlyincreases after the inlet.

FIG. 12 shows an embodiment of a shunt 148 having an inlet 149configured to receive fluid from an anterior chamber of an eye and anoutlet 150 configured to direct the fluid to a location of lowerpressure with respect to the anterior chamber, in which the body furtherincludes a variable inner diameter that increases along the length ofthe body from the inlet 149 to the outlet 150. In certain embodiments,the inner diameter continuously increases along the length of the body,for example as shown in FIG. 12. In other embodiments, the innerdiameter remains constant along portions of the length of the body.

In exemplary embodiments, the inner diameter may range in size fromabout 10 μm to about 200 μm, and the inner diameter at the outlet mayrange in size from about 15 μm to about 300 μm. The present disclosureencompasses shunts of different shapes and different dimensions, andsome embodiments of the shunts disclosed herein may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from about 10 μm to about 250 μm, an outside diameter fromabout 100 μm to about 450 μm, and a length from about 2 mm to about 10mm. Shunts of the invention may be made from any biocompatible material.An exemplary material is gelatin. Methods of making shunts composed ofgelatin are described above.

Shunts Having Pronged Ends

In other aspects, the present disclosure generally provides shunts forfacilitating conduction of fluid flow away from an organ, the shuntincluding a body, in which at least one end of the shunt is shaped tohave a plurality of prongs. Such shunts reduce probability of the shuntclogging after implantation because fluid can enter or exit the shunt byany space between the prongs even if one portion of the shunt becomesclogged with particulate.

FIGS. 13A-13D show embodiments of a shunt 152 in which at least one endof the shunt 152 includes a plurality of prongs 153 a-153 d. FIGS.13A-13D show embodiments in which both a proximal end and a distal endof the shunt are shaped to have the plurality of prongs. However,numerous different configurations are envisioned. For example, incertain embodiments, only the proximal end of the shunt is shaped tohave the plurality of prongs. In other embodiments, only the distal endof the shunt is shaped to have the plurality of prongs.

Prongs 153 a-153 d can have any shape (i.e., width, length, height).FIGS. 13A-13B show prongs 153 a-153 d as straight prongs. In thisembodiment, the spacing between the prongs 153 a-153 d is the same. Inanother embodiment shown in FIGS. 13C-13D, prongs 153 a-153 d aretapered. In this embodiment, the spacing between the prongs increasestoward a proximal and/or distal end of the shunt 152.

FIGS. 13A-13D show embodiments that include four prongs. However, someembodiments of the shunts disclosed herein may accommodate any number ofprongs, such as two prongs, three prongs, four prongs, five prongs, sixprongs, seven prongs, eight prongs, nine prongs, ten prongs, etc. Thenumber of prongs chosen will depend on the desired flow characteristicsof the shunt.

The present disclosure encompasses shunts of different shapes anddifferent dimensions, and some embodiments of the shunts disclosedherein may be any shape or any dimension that may be accommodated by theeye. In certain embodiments, the intraocular shunt is of a cylindricalshape and has an outside cylindrical wall and a hollow interior. Theshunt may have an inside diameter from about 10 μm to about 250 μm, anoutside diameter from about 100 μm to about 450 μm, and a length fromabout 2 mm to about 10 mm. Some embodiments of the shunts disclosedherein may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts Having a Longitudinal Slit

In other aspects, the present disclosure generally provides a shunt fordraining fluid from an anterior chamber of an eye that includes a hollowbody defining an inlet configured to receive fluid from an anteriorchamber of the eye and an outlet configured to direct the fluid to alocation of lower pressure with respect to the anterior chamber; theshunt being configured such that at least one end of the shunt includesa longitudinal slit. Such shunts reduce probability of the shuntclogging after implantation because the end(s) of the shunt can moreeasily pass particulate which would generally clog a shunt lacking theslits.

FIGS. 14A-14D show embodiments of a shunt 154 in which at least one endof the shunt 154 includes a longitudinal slit 155 that produces a topportion 156 a and a bottom portion 156 b in a proximal and/or distal endof the shunt 154. FIGS. 14A-14D show an embodiment in which both aproximal end and a distal end include a longitudinal slit 155 thatproduces a top portion 156 a and a bottom portion 156 b in both ends ofthe shunt 154. However, numerous different configurations areenvisioned. For example, in certain embodiments, only the proximal endof the shunt includes longitudinal slit 155. In other embodiments, onlythe distal end of the shunt includes longitudinal slit 155.

Longitudinal slit 155 can have any shape (i.e., width, length, height).FIGS. 14A-14B show a longitudinal slit 155 that is straight such thatthe space between the top portion 156 a and the bottom portion 156 bremains the same along the length of the slit 155. In another embodimentshown in FIGS. 14C-14D, longitudinal slit 155 is tapered. In thisembodiment, the space between the top portion 145 a and the bottomportion 156 b increases toward a proximal and/or distal end of the shunt154.

The present disclosure encompasses shunts of different shapes anddifferent dimensions, and the some embodiments of the shunts disclosedherein may be any shape or any dimension that may be accommodated by theeye. In certain embodiments, the intraocular shunt is of a cylindricalshape and has an outside cylindrical wall and a hollow interior. Theshunt may have an inside diameter from about 10 μm to about 250 μm, anoutside diameter from about 100 μm to about 450 μm, and a length fromabout 2 mm to about 10 mm. Some embodiments of the shunts disclosedherein may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Pharmaceutical Agents

In certain embodiments, some embodiments of the shunts disclosed hereinmay be coated or impregnated with at least one pharmaceutical and/orbiological agent or a combination thereof. The pharmaceutical and/orbiological agent may coat or impregnate an entire exterior of the shunt,an entire interior of the shunt, or both. Alternatively, thepharmaceutical or biological agent may coat and/or impregnate a portionof an exterior of the shunt, a portion of an interior of the shunt, orboth. Methods of coating and/or impregnating an intraocular shunt with apharmaceutical and/or biological agent are known in the art. See forexample, Darouiche (U.S. Pat. Nos. 7,790,183; 6,719,991; 6,558,686;6,162,487; 5,902,283; 5,853,745; and 5,624,704) and Yu et al. (U.S.Patent App. No. 2008/0108933). The content of each of these referencesis incorporated by reference herein its entirety.

In certain embodiments, the exterior portion of the shunt that residesin the anterior chamber after implantation (e.g., about 1 mm of theproximal end of the shunt) is coated and/or impregnated with thepharmaceutical or biological agent. In other embodiments, the exteriorof the shunt that resides in the scleral tissue after implantation ofthe shunt is coated and/or impregnated with the pharmaceutical orbiological agent. In other embodiments, the exterior portion of theshunt that resides in the intrascleral space after implantation iscoated and/or impregnated with the pharmaceutical or biological agent.In embodiments in which the pharmaceutical or biological agent coatsand/or impregnates the interior of the shunt, the agent may be flushedthrough the shunt and into the area of lower pressure (e.g., theintrascleral space).

Any pharmaceutical and/or biological agent or combination thereof may beused with some embodiments of the shunts disclosed herein. Thepharmaceutical and/or biological agent may be released over a shortperiod of time (e.g., seconds) or may be released over longer periods oftime (e.g., days, weeks, months, or even years). Exemplary agentsinclude anti-mitotic pharmaceuticals such as Mitomycin-C or5-Fluorouracil, anti-VEGF (such as Lucentis, Macugen, Avastin, VEGF orsteroids).

Deployment Devices

Any deployment device or system known in the art may be used with someembodiments of the methods disclosed herein. In certain embodiments,deployment into the eye of an intraocular shunt according to someembodiments can be achieved using a hollow shaft configured to hold theshunt, as described herein. The hollow shaft can be coupled to adeployment device or part of the deployment device itself. Deploymentdevices that are suitable for deploying shunts according to someembodiments include, but are not limited to the deployment devicesdescribed in U.S. Pat. No. 6,007,511, U.S. Pat. No. 6,544,249, U.S.Publication No. 2008/0108933, U.S. Patent App. No. 61/904,429, filed onNov. 14, 2013, and U.S. patent application Ser. No. 14/313,970, filed onJun. 24, 2013, the contents of which are each incorporated herein byreference in their entireties. In other embodiments, the deploymentdevices are devices as described in co-pending and co-owned U.S. patentapplication Ser. No. 12/946,222 filed on Nov. 15, 2010, or deploymentdevices described in co-pending and co-owned U.S. patent applicationSer. No. 12/946,645 filed on Nov. 15, 2010, the entire content of eachof which is incorporated by reference herein.

A shunt deployment device, such as those disclosed herein, can be usedto implant the shunt in accordance with a variety of potentialprocedures, which can be modified or updated, according to aspects ofthe disclosure herein, as well as future methodologies and devicefeatures. For example, as discussed and shown below with regard to FIGS.52A-54E, a shunt deployment device can be used to implant a shunt usinga variety of different procedures. The deployment device can be manualor automatic and can include features of one or more of the devicesdiscussed or mentioned herein.

For example, in some embodiments, the shunts can be deployed into theeye using the deployment device 200 depicted in FIG. 15. While FIG. 15shows a handheld, manually operated shunt deployment device, it will beappreciated that devices according to some embodiments may be coupledwith robotic systems and may be completely or partially automated. Asshown in FIG. 15, deployment device 200 includes a generally cylindricalbody or housing 201; however, the body shape of housing 201 could beother than cylindrical. Housing 201 may have an ergonomical shape,allowing for comfortable grasping by an operator. Housing 201 is shownwith optional grooves 202 to allow for easier gripping by a surgeon.

According to some embodiments, the shunt can be advanced into the eyetissue at a rate of between about 0.15 mm/sec to about 0.85 mm/sec.Further, in some embodiments, the shunt can be advanced into the eyetissue at a rate of between about 0.25 mm/sec to about 0.65 mm/sec.

Housing 201 is shown having a larger proximal portion that tapers to adistal portion. The distal portion includes a hollow sleeve 205. Thehollow sleeve 205 is configured for insertion into an eye and to extendinto an anterior chamber of an eye. The hollow sleeve 205 is visiblewithin an anterior chamber of an eye. According to some embodiment, thesleeve 205 can provide a visual preview or guide for an operator as toplacement of the proximal portion of the shunt within the anteriorchamber of an eye, as discussed below with regard to FIGS. 52A-52E. Thesleeve 205 can provide a visual reference point that may be used by anoperator to hold device 100 steady during the shunt deployment process,thereby assuring optimal longitudinal placement of the shunt within theeye.

According to some embodiments, the sleeve 205 may also include an edge231 at a distal end that provides resistance feedback to an operatorupon insertion of the deployment device 200 within an eye 232 of aperson during delivery of the shunt 215, as discussed below with regardto FIGS. 53A-54E. Upon advancement of the device 200 across an anteriorchamber 233 of the eye 232, the hollow sleeve 205 will eventuallycontact the anterior chamber angle tissue, and may abut sclera 234,providing resistance feedback to an operator that no further advancementof the device 200 is necessary. A temporary guard 208 is configured tofit around sleeve 205 and extend beyond an end of sleeve 205. The edge231 of the sleeve 205 prevents the shaft 204 from accidentally beingpushed too far through the sclera 234. The guard is used during shippingof the device and protects an operator from a distal end of a hollowshaft 204 that extends beyond the end of the sleeve 205. The guard isremoved prior to use of the device.

Housing 201 is open at its proximal end, such that a portion of adeployment mechanism 203 may extend from the proximal end of the housing201. A distal end of housing 201 is also open such that at least aportion of a hollow shaft 204 may extend through and beyond the distalend of the housing 201. Housing 201 further includes a slot 206 throughwhich an operator, such as a surgeon, using the device 200 may view anindicator 207 on the deployment mechanism 203.

Housing 201 may be made of any material that is suitable for use inmedical devices. For example, housing 201 may be made of a lightweightaluminum or a biocompatible plastic material. Examples of such suitableplastic materials include polycarbonate and other polymeric resins suchas DELRIN and ULTEM. In certain embodiments, housing 201 is made of amaterial that may be autoclaved, and thus allow for housing 201 to bere-usable. Alternatively, device 200 may be sold as a one-time-usedevice, and thus the material of the housing does not need to be amaterial that is autoclavable.

Housing 201 may be made of multiple components that connect together toform the housing. FIG. 16 shows an exploded view of deployment device200. In this figure, housing 201 is shown having three components 201 a,201 b, and 201 c. The components are designed to screw together to formhousing 201. FIGS. 17A-17D also show deployment mechanism 203. Thehousing 201 is designed such that deployment mechanism 203 fits withinassembled housing 201. Housing 201 is designed such that components ofdeployment mechanism 203 are movable within housing 201.

FIGS. 17A-17D show different enlarged views of the deployment mechanism203. Deployment mechanism 203 may be made of any material that issuitable for use in medical devices. For example, deployment mechanism203 may be made of a lightweight aluminum or a biocompatible plasticmaterial. Examples of such suitable plastic materials includepolycarbonate and other polymeric resins such as DELRIN and ULTEM. Incertain embodiments, deployment mechanism 203 is made of a material thatmay be autoclaved, and thus allow for deployment mechanism 203 to bere-usable. Alternatively, device 200 may be sold as a one-time-usedevice, and thus the material of the deployment mechanism does not needto be a material that is autoclavable.

Deployment mechanism 203 includes a distal portion 209 and a distalportion 210. The deployment mechanism 203 is configured such that distalportion 209 is movable within distal portion 210. More particularly,distal portion 209 is capable of partially retracting to within proximalportion 210.

In this embodiment, the distal portion 209 is shown to taper to aconnection with a hollow shaft 204. This embodiment is illustrated suchthat the connection between the hollow shaft 204 and the distal portion209 of the deployment mechanism 203 occurs inside the housing 201. Inother embodiments, the connection between hollow shaft 204 and thedistal portion 209 of the deployment mechanism 203 may occur outside ofthe housing 201. Hollow shaft 204 may be removable from the distalportion 209 of the deployment mechanism 203. Alternatively, the hollowshaft 204 may be permanently coupled to the distal portion 209 of thedeployment mechanism 203.

Generally, hollow shaft 204 is configured to hold an intraocular shunt,such as the intraocular shunts according to some embodiments. The shaft204 may be any length. A usable length of the shaft may be anywhere fromabout 5 mm to about 40 mm, and is about 15 mm in certain embodiments. Incertain embodiments, the shaft is straight. In other embodiments, shaftis of a shape other than straight, for example a shaft having a bendalong its length.

A proximal portion of the deployment mechanism includes optional grooves216 to allow for easier gripping by an operator for easier rotation ofthe deployment mechanism, which will be discussed in more detail below.The proximal portion 210 of the deployment mechanism also includes atleast one indicator that provides feedback to an operator as to thestate of the deployment mechanism. The indicator may be any type ofindicator known in the art, for example a visual indicator, an audioindicator, or a tactile indicator. FIGS. 17A and 17C show a deploymentmechanism having two indicators, a ready indicator 211 and a deployedindicator 219. Ready indicator 211 provides feedback to an operator thatthe deployment mechanism is in a configuration for deployment of anintraocular shunt from the deployment device 200. The ready indicator211 is shown in this embodiment as a green oval having a triangle withinthe oval. Deployed indicator 219 provides feedback to the operator thatthe deployment mechanism has been fully engaged and has deployed theshunt from the deployment device 200. The deployed indicator 219 isshown in this embodiment as a yellow oval having a black square withinthe oval. The indicators are located on the deployment mechanism suchthat when assembled, the indicators 211 and 219 may be seen through slot206 in housing 201.

The proximal portion 210 includes a stationary portion 210 b and arotating portion 210 a. The proximal portion 210 includes a channel 212that runs part of the length of stationary portion 210 b and the entirelength of rotating portion 210 a. The channel 212 is configured tointeract with a protrusion 217 on an interior portion of housingcomponent 201 a (FIGS. 18A and 18B). During assembly, the protrusion 217on housing component 201 a is aligned with channel 212 on the stationaryportion 210 b and rotating portion 210 a of the deployment mechanism203. The proximal portion 210 of deployment mechanism 203 is slid withinhousing component 201 a until the protrusion 217 sits within stationaryportion 210 b (FIG. 18C). Assembled, the protrusion 217 interacts withthe stationary portion 210 b of the deployment mechanism 203 andprevents rotation of stationary portion 210 b. In this configuration,rotating portion 210 a is free to rotate within housing component 201 a.

Referring back to FIGS. 17A-17D, the rotating portion 210 a of proximalportion 210 of deployment mechanism 203 also includes channels 213 a,213 b, and 213 c. Channel 213 a includes a first portion 213 a 1 that isstraight and runs perpendicular to the length of the rotating portion210 a, and a second portion 213 a 2 that runs diagonally along thelength of rotating portion 210 a, downwardly toward a proximal end ofthe deployment mechanism 203. Channel 213 b includes a first portion 213b 1 that runs diagonally along the length of the rotating portion 210 a,downwardly toward a distal end of the deployment mechanism 203, and asecond portion that is straight and runs perpendicular to the length ofthe rotating portion 210 a. The point at which first portion 213 a 1transitions to second portion 213 a 2 along channel 213 a, is the sameas the point at which first portion 213 b 1 transitions to secondportion 213 b 2 along channel 213 b. Channel 213 c is straight and runsperpendicular to the length of the rotating portion 210 a. Within eachof channels 213 a, 213 b, and 213 c, sit members 214 a, 214 b, and 214 crespectively. Members 214 a, 214 b, and 214 c are movable withinchannels 213 a, 213 b, and 213 c. Members 214 a, 214 b, and 214 c alsoact as stoppers that limit movement of rotating portion 210 a, whichthereby limits axial movement of the shaft 204.

FIG. 19 shows a cross-sectional view of deployment mechanism 203. Member214 a is connected to the distal portion 209 of the deployment mechanism203. Movement of member 214 a results in retraction of the distalportion 209 of the deployment mechanism 203 to within the proximalportion 210 of the deployment mechanism 203. Member 214 b is connectedto a pusher component 218. The pusher component 218 extends through thedistal portion 209 of the deployment mechanism 203 and extends into aportion of hollow shaft 204. The pusher component is involved indeployment of a shunt from the hollow shaft 204. An exemplary pushercomponent is a plunger. Movement of member 214 b engages pusher 218 andresults in pusher 218 advancing within hollow shaft 204.

Reference is now made to FIGS. 20A-22D, which accompany the followingdiscussion regarding deployment of a shunt 215 from deployment device200. FIG. 20A shows deployment device 200 in a pre-deploymentconfiguration. In this configuration, shunt 215 is loaded within hollowshaft 204 (FIG. 20C). As shown in FIG. 20C, shunt 215 is only partiallywithin shaft 204, such that a portion of the shunt is exposed. However,the shunt 215 does not extend beyond the end of the shaft 204. In otherembodiments, the shunt 215 is completely disposed within hollow shaft204. The shunt 215 is loaded into hollow shaft 204 such that the shuntabuts pusher component 218 within hollow shaft 204. A distal end ofshaft 204 is beveled to assist in piercing tissue of the eye.

Additionally, in the pre-deployment configuration, a portion of theshaft 204 extends beyond the sleeve 205 (FIG. 20C). The deploymentmechanism is configured such that member 214 a abuts a distal end of thefirst portion 213 a 1 of channel 213 a, and member 214 b abuts aproximal end of the first portion 213 b 1 of channel 213 b (FIG. 20B).In this configuration, the ready indicator 211 is visible through slot206 of the housing 201, providing feedback to an operator that thedeployment mechanism is in a configuration for deployment of anintraocular shunt from the deployment device 200 (FIG. 20A). In thisconfiguration, the device 200 is ready for insertion into an eye(insertion configuration or pre-deployment configuration). Methods forinserting and implanting shunts are discussed in further detail below.

Once the device has been inserted into the eye and advanced to alocation to where the shunt will be deployed, the shunt 215 may bedeployed from the device 200. The deployment mechanism 203 is atwo-stage system. The first stage is engagement of the pusher component218 and the second stage is retraction of the distal portion 209 towithin the proximal portion 210 of the deployment mechanism 203.Rotation of the rotating portion 210 a of the proximal portion 210 ofthe deployment mechanism 203 sequentially engages the pusher componentand then the retraction component.

In the first stage of shunt deployment, the pusher component is engagedand the pusher partially deploys the shunt from the deployment device.During the first stage, rotating portion 210 a of the proximal portion210 of the deployment mechanism 203 is rotated, resulting in movement ofmembers 214 a and 214 b along first portions 213 a 1 and 213 b 1 inchannels 213 a and 213 b. Since the first portion 213 a 1 of channel 213a is straight and runs perpendicular to the length of the rotatingportion 210 a, rotation of rotating portion 210 a does not cause axialmovement of member 214 a. Without axial movement of member 214 a, thereis no retraction of the distal portion 209 to within the proximalportion 210 of the deployment mechanism 203. Since the first portion 213b 1 of channel 213 b runs diagonally along the length of the rotatingportion 210 a, upwardly toward a distal end of the deployment mechanism203, rotation of rotating portion 210 a causes axial movement of member214 b toward a distal end of the device. Axial movement of member 214 btoward a distal end of the device results in forward advancement of thepusher component 218 within the hollow shaft 204. Such movement ofpusher component 218 results in partial deployment of the shunt 215 fromthe shaft 204.

FIGS. 21A-21C show schematics of the deployment mechanism at the end ofthe first stage of deployment of the shunt from the deployment device.As is shown FIG. 21A, members 214 a and 214 b have finished traversingalong first portions 213 a 1 and 213 b 1 of channels 213 a and 213 b.Additionally, pusher component 218 has advanced within hollow shaft 204(FIG. 21B), and shunt 215 has been partially deployed from the hollowshaft 204 (FIG. 21C). As is shown in these figures, a portion of theshunt 215 extends beyond an end of the shaft 204.

In the second stage of shunt deployment, the retraction component isengaged and the distal portion of the deployment mechanism is retractedto within the proximal portion of the deployment mechanism, therebycompleting deployment of the shunt from the deployment device. Duringthe second stage, rotating portion 210 a of the proximal portion 210 ofthe deployment mechanism 203 is further rotated, resulting in movementof members 214 a and 214 b along second portions 213 a 2 and 213 b 2 inchannels 213 a and 213 b. Since the second portion 213 b 2 of channel213 b is straight and runs perpendicular to the length of the rotatingportion 210 a, rotation of rotating portion 210 a does not cause axialmovement of member 214 b. Without axial movement of member 214 b, thereis no further advancement of pusher component 218. Since the secondportion 213 a 2 of channel 213 a runs diagonally along the length of therotating portion 210 a, downwardly toward a proximal end of thedeployment mechanism 203, rotation of rotating portion 210 a causesaxial movement of member 214 a toward a proximal end of the device.Axial movement of member 214 a toward a proximal end of the deviceresults in retraction of the distal portion 209 to within the proximalportion 210 of the deployment mechanism 203. Retraction of the distalportion 209, results in retraction of the hollow shaft 204. Since theshunt 215 abuts the pusher component 218, the shunt remains stationaryas the hollow shaft 204 retracts from around the shunt 215 (FIG. 21C).The shaft 204 retracts almost completely to within the sleeve 205.During both stages of the deployment process, the sleeve 205 remainsstationary and in a fixed position.

FIGS. 22A-22D show schematics of the device 200 after deployment of theshunt 215 from the device 200. FIG. 22B shows a schematic of thedeployment mechanism at the end of the second stage of deployment of theshunt from the deployment device. As is shown in FIG. 22B, members 214 aand 214 b have finished traversing along second portions 213 a 1 and 213b 1 of channels 213 a and 213 b. Additionally, distal portion 209 hasretracted to within proximal portion 210, thus resulting in retractionof the hollow shaft 204 to within the sleeve 205. FIG. 22D shows anenlarged view of the distal portion of the deployment device afterdeployment of the shunt. This figure shows that the hollow shaft 204 isnot fully retracted to within the sleeve 205 of the deployment device200. However, in certain embodiments, the shaft 204 may completelyretract to within the sleeve 205.

Methods for Intrascleral Shunt Placement

Some embodiments of the methods disclosed herein can involve creating anopening in the sclera (e.g., by piercing the sclera with a deliverydevice), and positioning a shunt in the anterior chamber of the eye suchthat the shunt terminates adjacent an opening formed in the sclera. Insome embodiments, such placement can permit flow through the shunt toreach the intrascleral space, thereby facilitating fluid flow throughboth the opening and the intrascleral space. The outlet of the shunt maybe positioned in different places within the intrascleral space. Forexample, the outlet of the shunt may be positioned within the sclera(e.g., within deep and superficial layers or tissue of the sclera).Alternatively, the outlet of the shunt may be positioned such that theoutlet is even with or superficial to the opening through the sclera.

Methods of implanting intraocular shunts are known in the art. Shuntsmay be implanted using an ab externo approach (entering through theconjunctiva and inwards through the sclera) or an ab interno approach(entering through the cornea, across the anterior chamber, through thetrabecular meshwork and sclera). The deployment device may be any devicethat is suitable for implanting an intraocular shunt into an eye. Suchdevices generally include a shaft connected to a deployment mechanism.In some devices, a shunt is positioned over an exterior of the shaft andthe deployment mechanism works to deploy the shunt from an exterior ofthe shaft. In other devices, the shaft is hollow and the shunt is atleast partially disposed in the shaft. In those devices, the deploymentmechanism works to deploy the shunt from within the shaft. Depending onthe device, a distal portion of the shaft may be sharpened or blunt, orstraight or curved.

Ab-Interno Approach

Ab interno approaches for implanting an intraocular shunt in thesubconjunctival space are shown for example in Yu et al. (U.S. Pat. No.6,544,249 and U.S. Patent Publication No. 2008/0108933) and Prywes (U.S.Pat. No. 6,007,511), the contents of each of which are incorporated byreference herein in its entirety. An exemplary ab-interno method employsa transpupil approach and involves creating a first opening in thesclera of an eye, advancing a shaft configured to hold an intraocularshunt across an anterior chamber of an eye and through the sclera tocreate a second opening in the sclera, retracting the shaft through thesecond opening to within the sclera (i.e., the intrascleral space),deploying the shunt from the shaft such that the shunt forms a passagefrom the anterior chamber of the eye to the intrascleral space of theeye, such that an outlet of the shunt is positioned so that at leastsome of the fluid that exits the shunt flows through the second openingin the sclera, and withdrawing the shaft from the eye. The first openingin the sclera may be made in any manner. In certain embodiments, theshaft creates the first opening in the sclera. In other embodiments, atool other than the shaft creates the first opening in the sclera.

In certain embodiments, some embodiments of the methods disclosed hereincan generally involve inserting into the eye a hollow shaft configuredto hold an intraocular shunt. In certain embodiments, the hollow shaftis a component of a deployment device that may deploy the intraocularshunt. The shunt is then deployed from the shaft into the eye such thatthe shunt forms a passage from the anterior chamber into the sclera(i.e., the intrascleral space). The hollow shaft is then withdrawn fromthe eye.

To place the shunt within the eye, a surgical intervention to implantthe shunt is performed that involves inserting into the eye a deploymentdevice that holds an intraocular shunt, and deploying at least a portionof the shunt within intrascleral space. FIGS. 23-30 provide an exemplarysequence for ab interno shunt placement. In certain embodiments, ahollow shaft 109 of a deployment device holding the shunt 112 enters theeye through the cornea (ab interno approach, FIG. 23). The shaft 109 isadvanced across the anterior chamber 110 in what is referred to as atranspupil implant insertion. The shaft 109 is advanced through theanterior angle tissues of the eye and into the sclera 8 and furtheradvanced until it passes through the sclera 8, thereby forming a secondopening in the sclera 8 (FIGS. 24-25). Once the second opening in thesclera 8 is achieved, the shaft 109 is retracted all the way backthrough the sclera 8 and into the anterior chamber 110 of the eye (FIGS.26-29). During this shaft retraction, the shunt 112 is held in place bya plunger rod 111 that is positioned behind the proximal end of theshunt 112. After the shaft 109 has been completely withdrawn from thesclera 8, the plunger rod 111 is withdrawn as well and the shuntimplantation sequence is complete (FIG. 30). This process results in animplanted shunt 112 in which a distal end of the shunt 112 is proximatea passageway 114 through the sclera 8. Once fully deployed, a proximalend of shunt 112 resides in the anterior chamber 110 and a distal end ofshunt 112 resides in the intrascleral space. Preferably a sleeve 113 isused around the shaft 112 and designed in length such that the sleeve113 acts as a stopper for the scleral penetration of the shaft and alsodetermines the longitudinal placement of the proximal end of the shunt.

Insertion of the shaft of the deployment device into the sclera 8produces a long scleral channel of about 2 mm to about 5 mm in length.Withdrawal of the shaft of the deployment device prior to deployment ofthe shunt 112 from the device produces a space in which the shunt 112may be deployed. Deployment of the shunt 112 allows for aqueous humor 3to drain into traditional fluid drainage channels of the eye (e.g., theintrascleral vein, the collector channel, Schlemm's canal, thetrabecular outflow, and the uveoscleral outflow to the ciliary muscle.The deployment is performed such that an outlet of the shunt ispositioned proximate the opening in the sclera so that at least some ofthe fluid that exits the shunt flows through the opening in the sclera,thereby ensuring that the intrascleral space does not become overwhelmedwith fluid output from the shunt.

FIG. 32 provides an exemplary schematic of a hollow shaft for use inaccordance with some embodiments of the methods disclosed herein. Thisfigure shows a hollow shaft 122 that is configured to hold anintraocular shunt 123. The shaft may hold the shunt within the hollowinterior 124 of the shaft, as is shown in FIG. 32. Alternatively, thehollow shaft may hold the shunt on an outer surface 125 of the shaft. Insome embodiments, the shunt is held completely within the hollowinterior of the shaft 124, as is shown in FIG. 32. In other embodiments,a shunt 123 a is only partially disposed within a hollow shaft 123 b, asshown in FIG. 4. Generally, in one embodiment, the intraocular shuntsare of a cylindrical shape and have an outside cylindrical wall and ahollow interior. The shunt may have an inside diameter of about 10 μm toabout 250 μm, an outside diameter of about 100 μm to about 450 μm, and alength of about 1 mm to about 12 mm. In some embodiments, the shunt hasa length of about 2 mm to about 10 mm and an outside diameter of about150 μm to about 400 μm. The hollow shaft 122 is configured to at leasthold a shunt of such shape and such dimensions. However, the hollowshaft 122 may be configured to hold shunts of different shapes anddifferent dimensions than those described above, and some embodimentscan encompass a shaft 122 that may be configured to hold any shaped ordimensioned intraocular shunt.

Preferably, some embodiments of the methods disclosed herein areconducted by making an incision in the eye prior to insertion of thedeployment device. In some embodiments of the methods disclosed hereinmay be conducted without making an incision in the eye prior toinsertion of the deployment device. In certain embodiments, the shaftthat is connected to the deployment device has a sharpened point or tip.In certain embodiments, the hollow shaft is a needle. Exemplary needlesthat may be used are commercially available from Terumo Medical Corp.(Elkington Md.). In some embodiments, the needle has a hollow interiorand a beveled tip, and the intraocular shunt is held within the hollowinterior of the needle. In another embodiment, the needle has a hollowinterior and a triple ground point or tip.

Some embodiments of the methods disclosed herein are preferablyconducted without needing to remove an anatomical portion or feature ofthe eye, including but not limited to the trabecular meshwork, the iris,the cornea, or aqueous humor. Some embodiments of the methods disclosedherein are also preferably conducted without inducing substantial ocularinflammation, such as subconjunctival blebbing or endophthalmitis. Suchmethods can be achieved using an ab interno approach by inserting thehollow shaft configured to hold the intraocular shunt through thecornea, across the anterior chamber, through the trabecular meshwork andinto the sclera. However, some embodiments of the methods disclosedherein may be conducted using an ab externo approach.

When some embodiments of the methods disclosed herein are conductedusing an ab interno approach, the angle of entry through the cornea aswell as the up and downward forces applied to the shaft during thescleral penetration affect optimal placement of the shunt in theintrascleral space. Preferably, the hollow shaft is inserted into theeye at an angle superficial to the corneal limbus, in contrast withentering through or deep to the corneal limbus. For example, the hollowshaft is inserted about 0.25 mm to about 3.0 mm, preferably about 0.5 mmto about 2.5 mm, more preferably about 1.0 mm to about 2.0 mmsuperficial to the corneal limbus, or any specific value within saidranges, e.g., about 1.0 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm,about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm,about 1.9 mm, or about 2.0 mm superficial to the corneal limbus.

Without intending to be bound by any theory, placement of the shuntfarther from the limbus at the exit site, as provided by an angle ofentry superficial to the limbus, as well as an S-shaped scleral tunnel(FIG. 31) due to applied up or downward pressure during the scleralpenetration of the shaft is believed to provide access to more lymphaticchannels for drainage of aqueous humor, such as the episcleral lymphaticnetwork, in addition to the conjunctival lymphatic system.

Ab Externo Approach

In other embodiments, an ab externo approach is employed. Ab externoimplantation approaches are shown for example in Nissan et al. (U.S.Pat. No. 8,109,896), Tu et al. (U.S. Pat. No. 8,075,511), and Haffner etal. (U.S. Pat. No. 7,879,001), the content of each of which isincorporated by reference herein in its entirety. An exemplary abexterno approach avoids having to make a scleral flap. In this preferredembodiment, a distal end of the deployment device is used to make anopening into the eye and into the sclera. For example, a needle isinserted from ab externo through the sclera and exits the anterior angleof the eye. The needle is then withdrawn, leaving a scleral slit behind.A silicone tube with sufficient stiffness is then manually pushedthrough the scleral slit from the outside so that the distal tube endsdistal to the Trabecular Meshwork in the anterior chamber of the eye.Towards the proximal end, the tube exits the sclera, lays on top of it,and connects on its proximal end to a plate that is fixated by suturesto the outside scleral surface far away (>10 mm) from the limbus.

FIGS. 33-39 describes another ab externo method that uses a deploymentdevice. In this method, a distal portion of the deployment deviceincludes a hollow shaft 109 that has a sharpened tip (FIG. 33). A shunt112 resides within the shaft 109. The distal shaft 109 is advanced intothe eye and into the sclera 8 until a proximal portion of the shaftresides in the anterior chamber 110 and a distal portion of the shaft109 is inside the scleral 8 (FIGS. 34-36). Deployment of the shunt 112that is located inside the shaft 109 is then accomplished by a mechanismthat withdraws the shaft 109 while the shunt 112 is held in place by aplunger 111 behind the proximal end of the shunt 112 (FIGS. 37-39). Asthe implantation sequence progresses, the shaft 109 is completelywithdrawn from the sclera 8. After that, the plunger 111 is withdrawnfrom the sclera 8, leaving the shunt 112 behind with its distal endinside the sclera 8, its proximal end inside the anterior chamber 110,and a passageway 114 through the sclera 8. In a preferred embodiment theshaft 109 is placed inside a sleeve 113 that is dimensioned in lengthrelative to the shaft 109 such that it will act as stopper during thepenetration of the shaft 109 into the eye and at the same time assurescontrolled longitudinal placement of the shunt 112 relative to the outersurface of the eye. The sleeve 113 may be beveled to match theanatomical angle of the entry site surface.

The shaft penetrates the conjunctival layer before it enters andpenetrates the sclera. This causes a conjunctival hole that could createa fluid leakage after the shunt placement has been completed. Tominimize the chance for any leakage, a small diameter shaft is used thatresults in a self-sealing conjunctival wound. To further reduce thechance for a conjunctival leak, a suture can be placed in theconjunctiva around the penetration area after the shunt placement.

Furthermore the preferred method of penetrating the conjunctiva isperformed by shifting the conjunctival layers from posterior to thelimbus towards the limbus, using e.g. an applicator such as a Q-tip,before the shaft penetration is started. This is illustrated in FIGS.40-41. That figure shows that an applicator 157 is put onto theconjunctiva 158, about 6 mm away from the limbus. The loose conjunctivalayer is then pushed towards the limbus to create folding tissue layersthat are about 2 mm away from the limbus. The device shaft 109 is nowinserted through the conjunctiva and sclera 8 starting about 4 mm awayfrom the limbus. After the shunt placement has been completed, the Q-tipis released and the conjunctival perforation relaxes back from about 4mm to about 8 mm limb at distance. This can cause the conjunctivalperforation to be 4 mm away from the now slowly starting drainage exit.This distance will reduce any potential for leakage and allows for afaster conjunctival healing response. Alternative to this describedupward shift, a sideway shift of the conjunctiva or anything in betweenis feasible as well. In another embodiment of the ab externo method, aconjunctival slit is cut and the conjunctiva is pulled away from theshaft entry point into the sclera. After the shunt placement iscompleted, the conjunctival slit is closed again through sutures.

In certain embodiments, since the tissue surrounding the trabecularmeshwork is optically opaque, an imaging technique, such as ultrasoundbiomicroscopy (UBM), optical coherence tomography (OCT) or a laserimaging technique, can be utilized. The imaging can provide guidance forthe insertion of the deployment device and the deployment of the shunt.This technique can be used with a large variety of shunt embodimentswith slight modifications since the trabecular meshwork is puncturedfrom the scleral side, rather than the anterior chamber side, in the abexterno insertion.

In another ab externo approach, a superficial flap may be made in thesclera and then a second deep scleral flap may be created and excisedleaving a scleral reservoir under the first flap. Alternatively, asingle scleral flap may be made with or without excising any portion ofthe sclera.

A shaft of a deployment device is inserted under the flap and advancedthrough the sclera and into an anterior chamber. The shaft is advancedinto the sclera until a proximal portion of the shaft resides in theanterior chamber and a distal portion of the shaft is in proximity tothe trabecular outflow. The deployment is then performed such that anoutlet of the shunt is positioned proximate the second opening in thesclera so that at least some of the fluid that exits the shunt flowsthrough the first opening in the sclera, thereby ensuring that theintrascleral space does not become overwhelmed with fluid output fromthe shunt. At the conclusion of the ab externo implantation procedure,the scleral flap may be sutured closed. The procedure also may beperformed without suturing.

Regardless of the implantation method employed, some embodiments of themethods disclosed herein recognize that the proximity of the distal endof the shunt to the scleral exit slit affects the flow resistancethrough the shunt, and therefore affects the intraocular pressure in theeye. For example, if the distal end of the shunt 112 is flush with thesclera surface then there is no scleral channel resistance (FIG. 42). Inthis embodiment, total resistance comes from the shunt 112 alone. Inanother embodiment, if the distal end of the shunt 112 is about 200 μmto about 500 μm behind the scleral exit, then the scleral slit closespartially around the exit location, adding some resistance to theoutflow of aqueous humor (FIG. 43). In another embodiments, if thedistal end of the shunt 112 is more than about 500 micron behind thescleral exit, than the scleral slit closes completely around the exitlocation with no backpressure and opens gradually to allow aqueous humorto seep out when the intraocular pressure raises e.g. above 10 mmHg(FIG. 44). The constant seepage of aqueous humor keeps the scleral slitfrom scaring closed over time.

Effectively, shunt placement according to some embodiments of themethods disclosed herein achieve a valve like performance where thescleral slit in front of the distal shunt end acts like a valve. Theopening (cracking) pressure of this valve can be adjusted by the outershunt diameter and its exact distal end location relative to the scleralexit site. Typical ranges of adjustment are 1 mmHg to 20 mmHg. Thispassageway distance can be controlled and adjusted through the design ofthe inserting device as well as the shunt length and the deploymentmethod. Therefore a specific design can be chosen to reduce or preventhypotony (<6 mmHg) as a post-operative complication.

FIGS. 45-51 illustrates placement of a shunt in various locations of theeye, according to some embodiments. In these figures, the first end of ashunt is positioned in the region of lower pressure and a second end ofthe shunt is positioned in a region of high pressure. For example, inFIG. 45, an end of a shunt 300 is shown extending into the anteriorchamber 1.

According to some embodiments of the methods disclosed herein, the shuntcan access the region of lower pressure by extending through theanterior chamber angle tissue. Thus, whether the shunt is targetingsupraciliary space, suprachoroidal space, the intrascleral space,intra-Tenon's adhesion space, or subconjunctival space, the shunt can beplaced through the anterior chamber angle tissue.

FIG. 45 illustrates supraciliary placement of a shunt 300. As shown, theshunt 300 extends from the anterior chamber 1 to the supraciliary space310. FIG. 46 illustrates suprachoroidal placement of a shunt 320. Asshown, the shunt 320 extends from the anterior chamber 1 to asuprachoroidal space 322. As discussed above, the supraciliary space 310can be continuous with the suprachoroidal space 322.

FIG. 47 illustrates subconjunctival placement of a shunt 330. As shown,the shunt 330 extends from the anterior chamber 1 to the subconjunctivalspace 332. FIG. 48 illustrates intrascleral placement of a shunt 340. Asshown, the shunt 340 extends from the anterior chamber 1 to theintrascleral space 342.

FIG. 49 depicts placement of a shunt 350 in the intra-Tenon's adhesionspace 11 of Tenon's capsule 10, according to some embodiments. As shown,the shunt 350 extends from the anterior chamber 1 to the intra-Tenon'sadhesion space 11. The shunt 350 can be passed through the sclera 8. Insome embodiments, the shunt 350 can extend at least partially throughSchlemm's canal 30 and/or the trabecular meshwork 32. Further, the shunt350 can extend through the trabecular meshwork 32 without passingthrough Schlemm's canal 30. Furthermore, the shunt 350 can extendentirely through the sclera 8 without passing through Schlemm's canal 30or the trabecular meshwork 32. This may be accomplished by passingthrough the sclera in a location posterior to Schlemm's canal 34anterior to the trabecular meshwork 32, above the scleral spur 36. Inaccordance with some embodiments, the shunt 350 can access theintra-Tenon's adhesion space 11 in a location anterior to the rectusmuscle 20. For example, a distal end of the shunt 350 can be positionedbetween the layers of intra-Tenon's adhesion space 11 anterior to therectus muscle 20.

FIG. 50 is an enlarged schematic cross-sectional view taken alongsection lines 50-50 of FIG. 49. As illustrated in FIG. 50, the shunt 350extends through the intra-Tenon's adhesion space 11. As shown, theintra-Tenon's adhesion space 11 comprises spongy, porous tissue(adhesions 352) that can facilitate drainage of aqueous humor from theanterior chamber.

When placing the shunt 350 into the intra-Tenon's adhesion space 11,some embodiments of the methods disclosed herein can comprise accessingthe intra-Tenon's adhesion space 11 by inserting a needle through a deeplayer 360 of Tenon's capsule 10 and positioning a distal end 362 of theshunt 350 into the intra-Tenon's adhesion space 11.

For example, the shunt 350 can enter intra-Tenon's adhesion space 11and, while maintaining the position of the needle (to avoid furtheradvancement of the needle into the intra-Tenon's adhesion space 11), theshunt 350 can then be urged distally into the intra-Tenon's adhesionspace 11 in order to preserve the adhesions 352 that extend between asuperficial layer 370 and the deep layer 360 of the Tenon's capsule 10.

In some embodiments, when the deep layer 360 is pierced, the shunt 350can be at least partially exposed beyond a distal tip of a needle andurged distally using a pusher component such that the shunt movesdistally out of the needle while maintaining the needle in a generallystationary position. For example, FIG. 51 illustrates that the distalend 362 of the shunt 350 can be urged distally such that the distal end362 passes between adjacent adhesions 352, which may cause the shunt 350to deflect, bend, and/or curve within the intra-Tenon's adhesion space11. Embodiments of such methods can thus be performed to allownon-destructive access to the intra-Tenon's adhesion space 11.

Deployment Device Motion Sequences

According to some embodiments, the deployment device can be operated torelease a shunt within the eye using a variety of motion sequences. Themotion sequences can be performed manually or automatically, with adevice. In some embodiments of the sequences discussed below, theoperator or clinician can perform a procedure using only two discretemotions: advancing the device into the eye until reaching a final stopposition and then, after the shunt has been implanted into the tissue,retracting the device from the eye. However, in accordance with someembodiments of the sequences discussed below, the operator or cliniciancan also exert a rotational force on one or more components of thedevice or on the device as a whole, to control advancement and releaseof the shunt. Further, in some embodiments of the sequences discussedbelow, the operator or clinician can perform the procedure using morethan two discrete axial motions, such as: advancing the device into theeye until reaching a preliminary stop position, and while implanting theshunt into the tissue, advancing the device toward a final stopposition; thereafter, when the shunt is implanted into the tissue, thedevice can be proximally withdrawn from the tissue. Additionally, insome embodiments of the sequences discussed below, the operator orclinician can exert axial and rotational forces on the device tofacilitate placement and release of the shunt.

Various procedures for releasing a shunt into the eye are discussedbelow with respect to FIGS. 52A-54E and aspects of this discussion canbe applied to more than one of the embodiments of the proceduresdiscussed herein. Such procedures allow a clinician to use a deploymentdevice to place the shunt precisely within the eye while minimizing anytrauma to the surrounding eye tissue.

As shown, FIGS. 52A-52E illustrate placement of a shunt into thesubconjunctival space. However, as discussed herein, the desiredlocation can be one of various anatomical locations within the eye,including, but not limited to the intrascleral space, thesubconjunctival space, and/or the intra-Tenon's adhesion space.According to some embodiments, the shunt can be positioned such that oneor more drainage outlets of the shunt extends within one or moreanatomical locations within the eye, such as a single anatomicallocation, or across multiple anatomical locations, thereby providingdrainage to either a single or multiple locations.

Further, according to some embodiments, the deployment device cancomprise a shaft that has a hard tip (e.g., to pierce the sclera forplacing the shunt, e.g., in the intrascleral space, the subconjunctivalspace, and/or the intra-Tenon's adhesion space) or a softer tip (e.g.,to advance the shunt, e.g., for placing the shunt in the supracilliaryspace and/or suprachoroidal space). Thus, although the embodimentsillustrated in FIGS. 52A-55E illustrate that placement of a shunt can bethrough or in sclera, other embodiments of an implantation procedure canbe performed such that the shunt is placed deep to a deep layer of thesclera.

According to some embodiments, a shunt can be loaded into the shaft suchthat a distal end portion of the shunt is positioned at the distal endof the shaft 410 (see e.g., FIGS. 23-30 and FIGS. 33-41).

FIGS. 52A-52E illustrate steps of a method in which a deployment device400 can be inserted into the eye 402 and provide a visual indication orguide for an operator during shunt placement. The device 400 can beadvanced across the anterior chamber 404 of the eye 402 until a needleor shaft 410 of the device 400 pierces the tissue at the anteriorchamber angle 412, referred to as anterior chamber angle tissue. Thedevice 400 can also comprise a sleeve 414 having a lumen in which theshaft 410 is disposed. The sleeve 414 can comprise a distal end 416 thatcan be visible within the anterior chamber 404 of the eye 402. Accordingto some embodiments, a mark or reference point on the sleeve 414, forexample, the distal end 416 of the sleeve 414, can provide a visualindication or guide for an operator during placement of the shunt, so asto locate or assess a final longitudinal position of the shunt.

For example, in some embodiments, such as those illustrated in FIGS.52A-52E and 54A-54E, the deployment device 400 can be configured suchthat when the shunt is being released from the device 400, a pushercomponent or plunger of the device 400 can distally advance the shuntrelative to the shaft 410 until the proximal end of the shunt isapproximately longitudinally adjacent to the distal end 416 of thesleeve 414. Thus, after the pusher component has been advanced to adesired position (e.g., to a position in which a distal end of thepusher component is proximal to, coextensive with, or distal to a distalend of the shaft 410) within the shaft 410, proximal retraction of theshaft 410 (while maintaining the sleeve 414 in a desired location) willrelease the shunt from the device 400 with the proximal end of the shuntbeing finally positioned about where the distal end 416 of the sleeve414 is positioned. While the relative positions of the distal end 416 ofthe sleeve 414 and the fully extended pusher component can varyaccording to some embodiments (e.g., contrast the embodiment shown inFIGS. 53A-53E), the visualization of the position of the distal end 416(or another marked aspect of the sleeve 414) can facilitate preciselongitudinal placement of the shunt within the eye tissue.

According to some embodiments, the mark or reference point of the sleeve414 can comprise the distal end 416 or a line extending crosswise on thesleeve 414 (proximal to the distal end 416). The mark or reference pointcan comprise a high contrast element or color to facilitatevisualization or discernment of the location of the marker referencepoint when the sleeve 414 is inserted into or toward an aspect of theeye, such as the anterior chamber 404 or anterior chamber angle 412.

Further, although a clinician can, in some embodiments, verify initialplacement of the device 400 with reference only to a mark, referencepoint, or position of the distal end 416 of the sleeve 414 relative toan aspect of the eye, such as the anterior chamber angle tissue oranterior chamber angle 412 itself, the initial placement or position ofthe device 400 can also be based on the position of the shaft 410 withinthe eye tissue. For example, for subconjunctival placement of the shunt420, as the shaft 410 is advanced through the sclera, a bevel 418 of theshaft 410 will eventually be seen through the conjunctiva (which istranslucent) as the bevel 418 exits the sclera. The clinician, based onthe visual confirmation of the location of the bevel below 418 theconjunctiva, can thereby determine that the shaft 410 has been advancedsufficiently. To avoid further advancement, which could result inpiercing or damaging the conjunctiva, the clinician can use the distalend 416 of the sleeve 414 to provide a visual indication or guidewhereby the clinician can maintain the position of the device 400 steadywithin the eye. Thus, the bevel 418 can be maintained in a positionadjacent to or opening to the subconjunctival space.

In some embodiments, such as that illustrated in FIGS. 52A-52E, as thedevice 400 is moved through the anterior chamber 404 and into initialposition within the eye tissue, the shaft 410 can be positioned relativeto the sleeve 414 such that the bevel 418 is spaced about 3 mm to about7 mm, about 4 mm to about 6 mm, or about 5 mm from the distal end 416 ofthe sleeve 414. Such spacing can allow the distal end 416 of the sleeve414 to be spaced apart from the anterior chamber angle tissue when thebevel 418 emerges from the sclera to become visible under theconjunctiva. Thus, the clinician can advantageously confirm properinitial placement of the device 400 by verifying bevel emergence fromthe sclera if it would otherwise be difficult to visually verify arelative positioning of the distal end 416 of the sleeve 414 and theanterior chamber angle tissue or anterior chamber angle 412. Thisprovides freedom to allow for variability in the anatomy and/ortrajectory of the advancing shaft 410 (e.g., for differences in thethickness of sclera from patient to patient).

After the device 400 has been advanced through the anterior chamber 404and the needle or shaft 410 has pierced the anterior chamber angletissue at the anterior chamber angle 412, the shunt 420 can be advancedsuch that a distal end portion 422 of the shunt 420 is moved into orpositioned at a desired location within the eye 402 (here shown as thesubconjunctival space 430).

The advancement of the distal end portion 422 of the shunt 420 into thedesired location of the eye 402 can be performed by advancing the pushercomponent (not shown) relative to the shaft 410 while maintaining theshaft 410 and the sleeve 414 steady, at a generally constant position orlocation, until the distal end portion 422 has been fully advanced intothe desired location, as illustrated in FIGS. 52B-52C. Thereafter, asshown in FIG. 52D, the shaft 410 can be proximally withdrawn relative tothe shunt 420. In some embodiments, the shaft 410 can also be proximallywithdrawn relative to the sleeve 414 and the pusher component whilemaintaining the sleeve 414 steady, at a generally constant position orlocation relative to the tissue. As the shaft 410 is proximallywithdrawn from the tissue of the eye 402, the pusher component maintainsthe longitudinal position of the shunt 420 in order to ensure that thedistal end portion 422 remains embedded at the desired location.Accordingly, proximal withdrawal of the shaft 410, while maintaining theposition of the shunt 420 in the eye 402, allows further exposure of theshunt 422 surrounding tissue.

Eventually, after the shunt 420 is released or embedded within the eyetissue, the shaft 410 can be fully withdrawn from covering or enclosingthe shunt 420, as shown in FIG. 52E. Further, in some embodiments, theshaft 410 can be completely retracted into the lumen of the sleeve 414,as also illustrated in FIG. 52E. The shaft 410 and the pusher componentcan be further withdrawn or retracted together into the lumen of thesleeve 414, as necessary. Thereafter, the device 400 can be proximallywithdrawn from the eye 402 and the procedure can be completed.

In accordance with some embodiments, the device 400 can also deliver theshunt 420 by allowing the distal end 416 of the sleeve 414 to contact orabut tissue within the eye. For example, the distal end 416 of thesleeve 414 can comprise one or more blunt structures, such as an edge,protrusion, and/or an annular, enlarged portion, that can be abuttedwith tissue of the eye 402, such as the anterior chamber angle tissue.

For example, referring to FIGS. 53A-53E, after the device 400 isadvanced into the anterior chamber 404, as discussed above with respectto FIG. 52A, the needle or shaft 410 can pierce the anterior chamberangle tissue. According to some embodiments, the device 400 can beadvanced until the distal end 416 of the shaft 414 abuts the anteriorchamber angle tissue of the anterior chamber angle 412. This abutmentcan provide resistance feedback to an operator, indicating that nofurther advancement of the device 400 is necessary. As discussed herein,the device 400 can comprise a blunt structure to prevent the shaft 410from accidentally being pushed too far through the eye tissue.

In some embodiments, such as that illustrated in FIGS. 53A-53E, as thedevice 400 is moved through the anterior chamber 404 and into initialposition within the eye tissue, the shaft 410 can be positioned relativeto the sleeve 414 such that the bevel 418 is spaced about 2 mm to about6 mm, about 3 mm to about 5 mm, or about 4 mm from the distal end 416 ofthe sleeve 414. Such spacing can tend to ensure that the distal end 416of the sleeve 414 is able to contact the anterior chamber angle tissueas the bevel 418 emerges from the sclera, but avoid piercing of thesclera.

Once the distal end 416 of the sleeve 414 is positioned abutting thetissue of the eye 402, the shunt 420 can be advanced distally, e.g., byusing a pusher component (not shown), until a distal end portion 430 ofthe shunt 420 is positioned at the desired location, as shown in FIG.53C. In some embodiments, such as that shown in FIGS. 53A-53E, theposition of the distal end 416 of the sleeve 414 relative to the fullyextended pusher component can be configured such that a maximum distaldisplacement or maximum distal position of the pusher component islongitudinally proximal to the sleeve distal end 416 when the pushercomponent is advanced within the shaft (see also FIGS. 23-30). Forexample, the pusher component can have a distalmost position of betweenabout 0 mm and about 8 mm, about 0 mm and about 4 mm, about 0 mm andabout 2 mm, or about 0 mm and about 1 mm proximal to the sleeve distalend.

Thereafter, once the shunt 420 is advanced to its final position, asshown in FIG. 53D, the shaft 410 can be proximally withdrawn relative tothe sleeve 414 to further expose the shunt 420 to surrounding tissue.Additionally, as shown in FIG. 53E, and as discussed above, the shaft410 can be fully withdrawn into the sleeve 414. Finally, the device 400can be removed from the eye and the procedure can be completed.

Further, in the embodiment illustrated in FIGS. 54A-54E, the device 400can be advanced through the anterior chamber 404 and the shaft 410 canpierce and enter eye tissue. The device 400 can be advanced until adistal end 416 of the sleeve 414 is positioned adjacent to or spacedapart from, but not abutting, the anterior chamber angle tissue or ispositioned within the anterior chamber angle 412 (a similar initialposition to that of FIG. 52B). Such a position can be a preliminary stopposition, as mentioned above, at which the clinician can ceaseadvancement of the device 400.

In such embodiments, after the device 400 has been initially placed inthe anterior chamber angle tissue or anterior chamber angle 412, theshunt 420 can be released by a motion sequence in which the shaft 410 ismaintained steady within the tissue while the distal end 416 of thesleeve 414 is advanced to abut the anterior chamber angle tissue, asdiscussed below. Such a motion can, in some embodiments, require thatthe operator or clinician further advance the device 400 axially untilreaching a final stop position, achieved when the distal end 416 of thesleeve 414 abuts the anterior chamber angle tissue. However, the device400 can also be configured to allow the sleeve 414 to move relative to ahousing of the device, thereby allowing the operator or clinician tomaintain the device 400 stationary relative to the face of the patientas the sleeve 414 is advanced further toward the anterior chamber angletissue.

As illustrated in FIGS. 54A-54B, the device 400 initially enters theanterior chamber 404 and is advanced until the shaft 410 pierces theanterior chamber angle tissue. The distal end 416 of the sleeve 414 canbe maintained or held spaced apart from the eye tissue or anteriorchamber angle 412, at an initial placement or position such as thatdiscussed above with respect to FIG. 52B. Although a clinician can, insome embodiments, verify initial placement of the device 400 withreference only to the position of the distal end 416 of the sleeve 414relative to the anterior chamber angle tissue or anterior chamber angle412, the initial placement or position of the device 400 can also bebased on the position of the shaft 410 within the eye tissue.

For example, as similarly discussed above, for subconjunctival placementof the shunt 420, the shaft 410 (and hence, the sleeve 414) will be atits proper location when a bevel 418 of the shaft 410 has exited oremerged from the sclera, but has not penetrated the conjunctiva. Thisemergence can be visually verified because the bevel 418 can be seenthrough or below the conjunctiva (which is translucent). Thereafter, theposition of the device 400 within the eye 402 can be maintained steadysuch that the bevel 418 remains positioned adjacent to or opening to thesubconjunctival space.

In such embodiments, such as that illustrated in FIGS. 54A-54E, as thedevice 400 is moved through the anterior chamber 404 and into initialposition within the eye tissue, the shaft 410 can be positioned relativeto the sleeve 414 such that the bevel 418 is spaced about 1 mm to about5 mm, about 2 mm to about 4 mm, or about 3 mm from the distal end 416 ofthe sleeve 414. Such spacing can allow the distal end 416 of the sleeve414 to be spaced apart from the eye tissue or anterior chamber angle 412when the bevel 418 emerges from the sclera. Thus, the clinician canadvantageously confirm proper initial placement of the device 400 byverifying bevel emergence from the sclera if it would otherwise bedifficult to visually verify a relative positioning of the distal end416 of the sleeve 414 and the tissue or anterior chamber angle 412. Thisprovides freedom to allow for variability in the anatomy and/ortrajectory of the advancing shaft 410.

Once initial placement of the device 400 is proper, the motion sequencecan continue by initiating relative movement between the shaft 410, thesleeve 414, and pusher component (not shown) to begin releasing theshunt 420.

As illustrated in FIGS. 54C-54D, after the device 400 reaches theinitial position, the shunt 420 can be distally advanced into the tissueuntil a distal end portion 430 reaches the desired location. Theadvancement of the distal end portion 422 of the shunt 420 into thedesired location of the eye 402 can be performed by advancing the pushercomponent (not shown) relative to the shaft 410 while maintaining theshaft 410 and the sleeve 414 steady, at a generally constant position orlocation

Further, as illustrated in FIG. 54D, the shaft 410 can be proximallywithdrawn into the sleeve 414. However, instead of maintaining thesleeve 414 at a generally constant position or location relative to theeye while the shaft 410 is withdrawn into the sleeve 414 (and incontrast to the embodiments discussed in FIGS. 52A-53E), the shaft 410can be obtained at a generally constant position relative to the eyetissue while the sleeve 414 moves relative to the eye tissue.

For example, the relative movement between the sleeve 414 and the shaft410 while the shaft 410 remains at a constant position relative to theeye tissue causes the sleeve 414 to be longitudinally advanced along theshaft 410, distally toward the eye tissue or anterior chamber angle 412.Thus, the sleeve 414 can move while the shaft 410 is held steady in theeye, at a generally constant position or location within the tissue.Accordingly, the sleeve 414 will be distally advanced toward theanterior chamber angle 412 until the distal end 416 of the sleeve 414contacts or abuts the eye tissue, such as the anterior chamber angletissue.

In some embodiments, the sleeve 414 can be advanced distally along theshaft 410 by about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm,about 6 mm, or more, as necessary, until contacting eye tissue.

For example, the sleeve distal end 416 can be distally advanced betweenabout 1 mm to about 4 mm or between about 2 mm to about 3 mm. The sleevecan be advanced at a rate of between about 0.15 mm/sec to about 0.85mm/sec, and in some embodiments, between about 0.25 mm/sec to about 0.65mm/sec.

When the distal end 416 abuts the eye tissue, further relativeretraction of the shaft 410 into the sleeve 414 will cause the shaft 410to be proximally withdrawn from the tissue because the distal end 416 ofthe sleeve 414 has now abutted the anterior chamber angle tissue, asillustrated in FIGS. 54D-54E. Continued retraction or withdrawal of theshaft 410 can cause the shaft 410 to be fully withdrawn into the lumenof the sleeve 414.

Aspects of the procedures discussed herein, including those discussedwith respect to FIGS. 52A-54E, can be implemented in various embodimentsof a procedure for implanting an intraocular shunt. The deploymentdevice can operate according to the features of any of the embodimentsdisclosed herein.

In any of the procedures discussed above with respect FIGS. 52A-54E,when the bevel 418 has been advanced through the sclera toward thesubconjunctival space, it may be necessary to further actuate the bevel418 in order to ensure that the subconjunctival space has been reachedand can be easily accessed by the shunt.

First, some clinicians may tend to conservatively advance the bevel 418within the sclera and fail to reach the subconjunctival space such thatthe bevel 418 is placed between the sclera and the conjunctiva. In suchsituations, when the bevel 418 has been advanced to a position shy ofthe subconjunctival space within the sclera, the bevel 418 can berotated within the sclera to permit the bevel 418 to “crack” the scleraand ensure that the subconjunctival space has been accessed. Therotation of the bevel 418 can cause the oblong or oval shape of thebevel 418 to rotate from a flat position to an upright position, therebypushing, breaking, or otherwise breaching the top surface of the scleraso that the lumen of the shaft 410 opens to the subconjunctival space toallow the shunt 420 to be advanced therefrom.

Second, in order to ensure that the subconjunctival space can be easilyaccessed by the shunt, even when the sclera has been breached in thesubconjunctival space has been accessed, rotating the bevel 418 cancause the conjunctiva to become “tented” or spaced apart from the topsurface of the sclera. This “tenting” of the conjunctiva can create apocket within the subconjunctival space. When advancing the shunt 420,the pocket will provide little frictional resistance or threat ofimpeding travel of the shunt 420 within the subconjunctival space.Accordingly, the shunt 420 can more readily begin its entry into thesubconjunctival space, thus avoiding kinking or bending of the shunt 420due to high frictional resistance that would otherwise be present absentthe creation of the pocket within the subconjunctival space.

Further teachings regarding the rotation or actuation of the bevel 418within the sclera are disclosed in Applicant's copending U.S. patentapplication Ser. No. 12/946,556, filed Nov. 15, 2010, the entirety ofwhich is incorporated herein by reference.

Further, the relative positioning of a shunt within the shaft and therange of movement of the pusher component within the shaft can beselectively modified to optimize the position of the shunt end portionswhen performing the motion sequences of the deployment device. Inparticular, to ensure proper placement of the distal end portion of theshunt, the maximum distal or fully advanced position of the pushercomponent relative to the sleeve distal end can be optimized.

For example, as noted above, the pusher component can have a maximumdistal displacement or maximum distal position that results in thepusher component being positioned at least longitudinally adjacent to(longitudinally coextensive with) the sleeve distal end or distallybeyond the sleeve distal end when the distal end of the sleeve distalend is maintained spaced apart from the eye tissue (e.g., spaced apartfrom the anterior chamber angle tissue), when the pusher component isadvanced within the shaft (see FIGS. 33-41, FIGS. 52B-52C, and FIGS.54B-54C). For example, the pusher component can have a distalmostposition of between 0 mm and about 8 mm, about 0 mm and about 4 mm,about 0 mm and about 2 mm, or about 0 mm and about 1 mm beyond or distalto the sleeve distal end.

Further, as noted above, the pusher component can have a maximum distaldisplacement or maximum distal position that results in the pushercomponent being positioned longitudinally proximal to the sleeve distalend when the pusher component is advanced within the shaft (see FIGS.23-30 and FIGS. 53B-53C). For example, the pusher component can have adistalmost position of between about 0 mm and about 8 mm, about 0 mm andabout 4 mm, about 0 mm and about 2 mm, or about 0 mm and about 1 mmproximal to the sleeve distal end.

The foregoing description is provided to enable a person skilled in theart to practice the various configurations described herein. While thesubject technology has been particularly described with reference to thevarious figures and configurations, it should be understood that theseare for illustration purposes only and should not be taken as limitingthe scope of the subject technology.

There may be many other ways to implement the subject technology.Various functions and elements described herein may be partitioneddifferently from those shown without departing from the scope of thesubject technology. Various modifications to these configurations willbe readily apparent to those skilled in the art, and generic principlesdefined herein may be applied to other configurations. Thus, manychanges and modifications may be made to the subject technology, by onehaving ordinary skill in the art, without departing from the scope ofthe subject technology.

It is understood that the specific order or hierarchy of steps in theprocesses disclosed is an illustration of exemplary approaches. Basedupon design preferences, it is understood that the specific order orhierarchy of steps in the processes may be rearranged. Some of the stepsmay be performed simultaneously. The accompanying method claims presentelements of the various steps in a sample order, and are not meant to belimited to the specific order or hierarchy presented.

Terms such as “top,” “bottom,” “front,” “rear” and the like as used inthis disclosure should be understood as referring to an arbitrary frameof reference, rather than to the ordinary gravitational frame ofreference. Thus, a top surface, a bottom surface, a front surface, and arear surface may extend upwardly, downwardly, diagonally, orhorizontally in a gravitational frame of reference.

Furthermore, to the extent that the term “include,” “have,” or the likeis used in the description or the claims, such term is intended to beinclusive in a manner similar to the term “comprise” as “comprise” isinterpreted when employed as a transitional word in a claim.

The word “exemplary” is used herein to mean “serving as an example,instance, or illustration.” Any embodiment described herein as“exemplary” is not necessarily to be construed as preferred oradvantageous over other embodiments.

A reference to an element in the singular is not intended to mean “oneand only one” unless specifically stated, but rather “one or more.”Pronouns in the masculine (e.g., his) include the feminine and neutergender (e.g., her and its) and vice versa. The term “some” refers to oneor more. Underlined and/or italicized headings and subheadings are usedfor convenience only, do not limit the subject technology, and are notreferred to in connection with the interpretation of the description ofthe subject technology. All structural and functional equivalents to theelements of the various configurations described throughout thisdisclosure that are known or later come to be known to those of ordinaryskill in the art are expressly incorporated herein by reference andintended to be encompassed by the subject technology. Moreover, nothingdisclosed herein is intended to be dedicated to the public regardless ofwhether such disclosure is explicitly recited in the above description.

While certain aspects and embodiments of the inventions have beendescribed, these have been presented by way of example only, and are notintended to limit the scope of the inventions. Indeed, the novel methodsand systems described herein may be embodied in a variety of other formswithout departing from the spirit thereof. The accompanying claims andtheir equivalents are intended to cover such forms or modifications aswould fall within the scope and spirit of the inventions.

What is claimed is:
 1. A method of treating glaucoma comprising:inserting a shaft of an inserter device into eye tissue, the devicesupporting an intraocular shunt and comprising a sleeve that extendsabout at least a portion of the shaft; advancing the shaft untilreaching a first position at which (i) a bevel of the shaft is in aspace adjacent to Tenon's capsule and (ii) a distal end of the sleeve isspaced apart from the eye tissue; releasing the shunt from the shaftsuch that an inflow end of the shunt is positioned in an anteriorchamber of the eye and an outflow end of the shunt is positioned in aspace in contact with Tenon's capsule; advancing the sleeve distallyover the shaft until the sleeve distal end contacts the eye tissue; andwithdrawing the shaft and sleeve from the eye.
 2. The method of claim 1,wherein the inserting further comprises introducing the shunt into theeye through a cornea of the eye.
 3. The method of claim 1, wherein theinserting comprises advancing the shaft into sclera until reaching andno further than the first position.
 4. The method of claim 3, whereinafter reaching the first position, the releasing comprises advancing apusher component of the device such that the shunt is pushed distallyout of the shaft.
 5. The method of claim 4, wherein the advancing thepusher component comprises pushing less than an entire length of theshunt distally out of the shaft.
 6. The method of claim 4, wherein theinserting further comprises advancing the pusher component to adistalmost position at which a distal end of the pusher component ispositioned longitudinally proximal to the sleeve distal end.
 7. Themethod of claim 4, wherein the sleeve comprises a lumen, the shaft beingdisposed within the lumen.
 8. The method of claim 7, wherein theinserting further comprises advancing the pusher component until adistal end of the pusher component is positioned longitudinally adjacentto the sleeve distal end.
 9. The method of claim 1, wherein the sleevedistal end is spaced apart from anterior chamber angle tissue in thefirst position.
 10. The method of claim 1, wherein the advancing thesleeve occurs while maintaining the shaft fixed relative to the eyetissue.
 11. The method of claim 10, wherein after the sleeve distal endcontacts the eye tissue, the releasing further comprises proximallywithdrawing the shaft from the eye tissue until the bevel is receivedwithin the sleeve.
 12. The method of claim 1, wherein at the firstposition, the bevel of the shaft is positioned between layers of Tenon'scapsule to position the shunt outflow end between the layers of Tenon'scapsule.
 13. The method of claim 1, wherein the releasing comprisespositioning the shunt outflow end deep to Tenon's capsule.
 14. Themethod of claim 1, wherein the releasing comprises positioning the shuntoutflow end in a subconjunctival space.
 15. The method of claim 1,wherein the device further comprises a plunger disposed within a lumenof the shaft to abut the shunt, and wherein the releasing furthercomprises, while maintaining the bevel stationary relative to the eyetissue, advancing the sleeve and the plunger relative to the shaft untilthe sleeve distal end contacts the eye tissue.
 16. A method of treatingglaucoma comprising: advancing a shaft of a device into eye tissue untila bevel of the shaft reaches a target area and a sleeve of the device isspaced apart from the eye tissue, the shaft supporting an intraocularshunt; advancing the shunt from the shaft into the target area; whilemaintaining the bevel stationary relative to the target area, advancingthe sleeve distally over the shaft until a distal end of the sleevecontacts the eye tissue; and upon contacting the sleeve distal end withthe eye tissue, proximally withdrawing the shaft from the eye tissue.17. The method of claim 16, further comprising, while maintaining thebevel stationary relative to the target area, advancing a plunger withinthe shaft to advance the shunt from the bevel until the shunt extendsinto the target area.
 18. The method of claim 17, wherein the advancingthe plunger further comprises pushing less than an entire length of theshunt distally out of the shaft.
 19. The method of claim 17, wherein theadvancing the plunger further comprises advancing the plunger until adistal end of the plunger is positioned longitudinally adjacent to thesleeve distal end.
 20. The method of claim 16, wherein the advancing theshaft comprises introducing the shaft through a cornea of the eye. 21.The method of claim 16, wherein the target area comprises supraciliaryspace, suprachoroidal space, a space between layers of sclera, a spacebetween layers of Tenon's capsule, or subconjunctival space.
 22. Themethod of claim 16, wherein the advancing the sleeve comprises advancingthe sleeve between about 1 mm to about 4 mm.
 23. The method of claim 22,wherein the advancing the sleeve comprises advancing the sleeve betweenabout 2 mm to about 3 mm.
 24. The method of claim 16, wherein the devicefurther comprises a plunger disposed within a lumen of the shaft to abutthe shunt, and wherein the advancing comprises advancing the sleeve andthe plunger relative to the shaft until the sleeve distal end contactsthe eye tissue.